Pesticidal 1-arylpyrazoles

ABSTRACT

The invention relates to novel 1-arylpyrazole oxime derivatives, of general formula (I) or (I bis)These compounds are found to be generally safe systemic insecticides for control of arthropod, nematode, helminth or protozoan pests including compositions and derivatives thereof.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a Division of Ser. No. 09/970,667 filed Oct. 5, 2001now U.S. Pat. No. 6,500,850 which is a continuation of Ser. No.09/450,450, filed Nov. 30, 1999, now abandoned, which is a Division ofSer. No. 08/989,247, filed Dec. 12, 1997 now U.S. Pat. No. 6,350,771which is a continuation-in-part of earlier U.S. patent application Ser.No. 08/946,375, filed Oct. 7, 1997, now abandoned, which claims thepriority of U.S. Provisional Patent Application No. 60/033,888, filedDec. 24, 1996, both of which are incorporated by reference herein intheir entireties and relied upon.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to novel 1-arylpyrazolecarboxaldehydeoximes, compositions, and derivatives thereof. It relates to theirunexpected and useful systemic insecticidal activity. The inventionparticularly pertains to compositions of said compounds and methods,using said compounds, for the control of arthropod, nematode, helminthor protozoan pests. In particular to the application of said compoundsor compositions in agricultural methods of use, particularly aspesticides, for controlling arthropods, especially insects by systemicaction. The invention also relates to 1-arylpyrazole hydrazones.

2. Description of the Related Art

The control of insects, nematodes or helminths by means of activematerial having a 1-arylpyrazole group therein has been described bymany patents or patent application such as International PatentPublication No. WO 93/06089 (and the equivalent U.S. Pat. No.5,451,598), WO 94/21606 and WO 87/03781 as well as in European PatentPublication Numbers 0295117, 659745, 679650, 201852 and 412849, GermanPatent No. DE19511269 and U.S. Pat. No. 5,232,940.

Other compounds are disclosed in WO 92/13451, Aug. 20, 1992, to ScheringAgrochemicals Ltd., which describes5-chloro-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(4,5-dicyano-1H-imadazol-2-yl)-3-hydroxyiminomethyl-1H-pyrazoleas an intermediate, also with activity against a single species Luciliasericata, sleep blow fly.

This Schering reference appears to be the only reference describing1-arylpyrazole-oxime compounds as insecticides.

It is an object of the present invention to provide new pesticidalcompounds of the 1-arylpyrazole family together with processes for theirpreparation.

A second object of the present invention is to provide pesticidalcompositions and pesticidal methods of use of the pesticidal pyrazolecompounds against arthropods, especially insects, plant nematodes, orhelminth or protozoan pests, particularly in agricultural orhorticultural crops, forestry, veterinary medicine or livestockhusbandry, or in public health.

A third object of the present invention is to provide very activecompounds, with broad spectrum pesticidal activity, as well as compoundswith selective special activity, e.g., aphicidal, miticidal, foliarinsecticidal, soil insecticidal and nematicidal, systemic, antifeedingor pesticidal activity via seed treatment.

A fourth object of the present invention is to provide compounds withsubstantially enhanced and more rapid.activity, especially againstinsects and more particularly insects in their larval stages.

A fifth object of the present invention is to provide compounds withgreatly improved (greater and faster) penetration into pest species whentopically applied and thus provide enhanced movement of the compounds tothe pesticidal site(s) of action within the pest.

Another object of the present invention is to provide compounds withhigh. activity and improved safety to the user and the environment.

These and other objects of the invention shall become readily apparentfrom the detailed description of the present invention. These objectsare met in whole or in part by the instant invention.

SUMMARY OF THE INVENTION

This invention describes novel systemic chemical compositions andmethods for treating plants with the compositions having insecticidal ornematocidal systemic activity of the following formula (I):

wherein:

X is —S(O)_(m)R₆ or R₇,

Y is hydrogen, C-3 to C-6 alkenyl, alkynyl, formyl, alkylcarbonyl,cycloalkylcarbonyl, halocycloalkyl carbonyl, aroyl, arylalkylcarbonyl,alkylsulfonyl, arylsulfonyl, haloalkylcarbonyl, aminoalkylcarbonyl,alkylaminoalkylcarbonyl, dialkylaminoalkylcarbonyl, alkoxyalkylcarbonyl,aryloxyalkylcarbonyl, alkylthioalkylcarbonyl,alkylsulfonylalkylcarbonyl, arylthioalkylcarbonyl, N-alkylcarbamoyl,N-arylcarbamoyl, N-alkylthiocarbamoyl, N-arylthiocarbamoyl,alpha-hydroxyarylalkylcarbonyl, hydroxyalkylcarbonyl,carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, —P(═O)(O-Alkyl)₂,—P(═S)(O-alkyl)₂, —P(═O)(S-alkyl)₂, —P(═S)(S-alkyl)₂, trialkylsilyl,alkylcarbonylaminoalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl,pyridinyl, pyrimidinyl, —C(═O)S-alkyl, —C(═O)S-aryl, —C(═O)S-alkylaryl,alkoxyalkoxycarbonyl, alkylthioalkoxycarbonyl,alkylsulfonylalkoxycarbonyl, arylthioalkoxycarbonyl, alkoxycarbonyl,aryloxycarbonyl and aryloxycarbonylalkylcarbonyl; or alkyl or haloalkyl,optionally substituted by alkoxy, alkoxycarbonyl, carboxy, cyano,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthio,nitro, alkylsulfinyl, alkylsulfonyl, alkylcarbonyl, amino, alkylamino,dialkylamino, hydroxy, alkylcarbonylamino or alkylcarbonyloxy;

Z is hydrogen, halogen, —C(O)R₇—, —S(O)_(n)R₈, —C(O)OR₉, alkyl,haloalkyl, —OR₉, —N═C(R₁₀)(R₁₁) alkenyl, hydrazino, alkylthiocarbonyl,1H-pyrrol-1-yl or 1H-pyrazol-1-yl, —CHO, —CH═NOH, amino, R₁₂NH— orR₁₃R₁₄N—;

R₁ is hydrogen, alkyl or —NR₁₅R₁₆;

R₂ is hydrogen or halogen;

R₃ and R₅ are hydrogen, halogen or alkyl;

R₄ is halogen, haloalkyl, haloalkoxy, R₁₇S(O)_(p)— or SF₅;

R₆ is alkyl or haloalkyl, alkenyl or haloalkenyl, alkynyl or haloalkynylor cycloalkyl having 3 to 5 carbon atoms;

R₇ is alkyl or haloalkyl;

R₈ is R₇ or phenyl;

R₉ and R₁₀ are hydrogen, alkyl or haloalkyl;

R₁₁ is alkyl, haloalkyl, alkoxy, or a phenyl group which is optionallysubstituted by one or more groups selected from hydroxy, halogen,alkoxy, cyano, R₇ or —S(O)_(q)R₇;

R₁₂, R₁₃ and R₁₄, which are identical or different, are R₇S(O)_(r)—,formyl, alkynyl, alkoxycarbonyl, alkylthiocarbonyl or aroyl; or alkyl,C-3 to C-6 alkenyl or —C(O)alkyl wherein the alkyl and alkenyl portionsare optionally substituted by one or more R₁₈; or R₁₃ and R₁₄ are joinedso as together form a divalent radical having 4 to 6 atoms in the chain,this divalent radical being alkylene, alkyleneoxyalkylene oralkyleneaminoalkylene, preferably to form a morpholine, pyrrolidine,piperidine or piperazine ring;

R₁₅ and R₁₆ are independently hydrogen or alkyl;

R₁₇ represents haloalkyl;

R₁₈ is cyano, nitro, alkoxy, haloalkoxy, —C(O)R₇, R₈S(O)_(s)—, —C(O)OR₉,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, halogen,hydroxy, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl;

m, n, p, q, r and s represent zero, one or two;

M is C-halo, C—CH₃, C—CH₂F, C—CH₂Cl, C—NO₂, or N;

geometric isomers, tautomeric forms and pesticidally active saltsthereof.

By the term “pesticidally acceptable salts” is meant salts the anionsand cations of which are known and accepted in the art for the formationof pesticidally acceptable salts. Preferably such salts are watersoluble. Suitable acid addition salts formed from compounds of formula(I) containing an amine group, include salts with inorganic acids forexample hydrochlorides, phosphates, sulfates and nitrates, and saltswith organic acids for example acetates. Suitable base addition saltsformed from compounds of formula (I) containing a carboxylic acid group,include alkali metal (for example sodium or potassium) salts, ammoniumsalts and organic amine (for example diethanolamine or morpholine)salts.

Compounds of formula (I) wherein R₁ represents —NR₁₅R₁₆ in which R₁₆represents hydrogen and R₁₅ represents hydrogen or alkyl may exist intautomeric forms as shown in formulae (Ia) and (Ib). Such tautomerism iswell known as is described in S.Patai (The Chemistry of FunctionalGroups: Amidines and Imidates, Vol 2, 1991, pages 276-277). It will beunderstood that all such tautomeric forms are embraced by the presentinvention.

Unless otherwise specified alkyl, alkoxy and alkylthio groups have fromone to six (preferably one to four) carbon atoms, alkenyl groups havefrom two to six (preferably two to four) carbon atoms and alkynyl groupshave from three to six (preferably three or four) carbon atoms.Cycloalkyl groups have from 3 to 8 carbon atoms, preferably 5 to 7carbon atoms. By the term “aryl” is meant mono or polycyclic aromaticmoieties, preferably including phenyl, pyridyl, pyrimidinyl, furyl andnaphthyl groups. It shall be understood that the rings formed by thedivalent alkylene radicals which include the nitrogen atoms to whichthey are attached are generally 5, 6 and 7 membered rings. In theinstant invention, some words are used in a specific sense: The term“aminocarbonyl” means a carbamoyl radical, that is, a radical of theformula —C(O)NH₂. Similarly, the term “alkylaminocarbonyl” means analkylcarbamoyl radical, that is, a radical of the formula—C(O)—NH-alkyl; and the term “dialkylaminocarbonyl” means adialkylcarbamoyl radical, that is, a radical of the formula—C(O)—N(alkyl)₂ in which the alkyl moieties can be the same ordifferent. The term “aminosulfonyl” means a sulfamoyl radical, that is,—SO₂NH₂. Similarly, the term “alkylaminosulfonyl” means analkylsulfamoyl radical, that is, a radical of the formula —SO₂NH-alkyl;while the term “dialkylaminosulfonyl”, means a dialkylsulfamoyl radical,which has the formula —SO₂N(alkyl)₂ wherein the alkyl moieties can bethe same or different.

The term “halo” before the name of a radical means that this radical ispartially or completely halogenated, that is to say, substituted by F,Cl, Br, or I, in any combination, preferably by F or Cl. The term“halogen” means F, Cl, Br or I. When the name of any substituent isrepeated, it keeps the same meaning unless otherwise specified. The term“aroyl” designates a carbonyl aromatic radical, that is, aryl-C(O)—,which is preferably a benzoyl optionally substituted by one or morealkyl, alkoxy or halogen groups.

Compounds in which Z is amino, R₁₂NH— or R₁₃R₁₄N— are preferred.

Compounds in which X is —S(O)_(m)R₆ are preferred.

R₁ is preferably amino or hydrogen;

R₆ is preferably alkyl; especially preferred are methyl and ethyl;

R₃ and R₅ are preferably hydrogen;

R₄ is preferably haloalkyl, haloalkoxy or SF₅; especially preferred istrifluoromethyl.

M is preferably C-halo, or N.

Y is preferably hydrogen or alkoxycarbonyl.

Preferred phenyl groups or pyridyl groups comprising the R₂ to R₅ and Mradicals in formula (I) are: 2,6-dichloro-4-trifluoromethylphenyl;2,6-dichloro-4-trifluoromethoxyphenyl;2-bromo-6-chloro-4-trifluoromethylphenyl;2-bromo-6-chloro-4-trifluoromethoxyphenyl;2,6-difluoro-4-trifluoromethylphenyl; 2-chloro-4-trifluoromethylphenyl;3-chloro-5-trifluoromethyl-2-pyridinyl;3-chloro-5-trifluoromethoxy-2-pyridinyl;2-bromo-6-fluoro-4-difluoromethylphenyl;2-chloro-6-fluoro-4-trifluoromethylphenyl;2,6-dibromo-4-trifluoromethylphenyl;2,6-dibromo-4-trifluoromethoxyphenyl; and2,6-dichloro-4-pentafluorothiophenyl.

A preferred class of compounds of formula (I) are those wherein:

X is —S(O)_(m)R₆;

Y is hydrogen; alkyl having 1 to 4 carbon atoms (including linear,branched and cyclic) optionally substituted by aminocarbonyl,alkylsulfonyl, alkoxy, alkoxycarbonyl, alkylcarbonyl, cyano or nitro;C-3 to C-4 alkenyl; C-3 to C-5 alkynyl; alkylcarbonyl; optionallysubstituted aroyl; arylalkylcarbonyl; alkylsulfonyl;alkoxycarbonylalkylcarbonyl; haloalkylcarbonyl; N-alkylcarbamoyl;alkoxycarbonyl; aryloxycarbonyl; alkoxyalkylcarbonyl;alpha-hydroxyarylalkylcarbonyl; hydroxyalkylcarbonyl;aminoalkylcarbonyl; —C(═O)S-alkyl and trialkylsilyl;

Z is amino, R₁₂NH—, R₁₃R₁₄N—, halogen or methyl;

R₁ is hydrogen, methyl, amino or methylamino;

R₂ is F, Cl, Br or H;

R₃ and R₅ are hydrogen;

R₄ is CF₃, CF₃O, CHF₂, CF₃S(O)_(p), CF₂Cl, CFCl₂, CF₂ClO, CFCl₂O, Cl,Br, or F;

R₆ is methyl or ethyl optionally substituted by F, Cl or Br;

M is CCl, CF, CBr, or N;

R₁₂, R₁₃ and R₁₄ are CF₃S(O)_(r)—, alkynyl or alkoxycarbonyl;

or alkyl, C-3 to C-6 alkenyl or —C(O)alkyl wherein the alkyl and alkenylportions are optionally substituted by one or more R₁₈; and

R₁₈ is cyano, nitro, alkoxy, haloalkoxy, —C(O)R₇, R₈S(O)_(s)—, —C(O)OR₉,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, halogen,hydroxy, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl.

A further preferred class of compounds of formula (I) are those wherein:

Y represents hydrogen; a C₁ to C₃ alkyl group optionally substituted bycyano, carbamoyl, carboxy, alkoxycarbonyl, alkylthio, alkylsulfinyl oralkylsulfonyl; trialkylsilyl; acetyl; propionyl substituted byalkoxycarbonyl; benzoyl optionally substituted by alkyl; alkoxycarbonyl;or N-alkylcarbamoyl;

Z represents amino, R₁₂NH—, R₁₃R₁₄N—, —CHO, —CH═NOH, halogen or methyl;

R₁ represents hydrogen, methyl, amino or methylamino;

R₂ represents chlorine, bromine or hydrogen;

R₃ and R₅ represent hydrogen;

R₄ represents CF₃ or OCF₃;

R₆ represents optionally halogenated methyl or ethyl;

R₇ represents CF₃;

R₁₂, R₁₃ and R₁₄ represent alkynyl; or methyl or ethyl optionallysubstituted by R₈S(O)_(s)—, cyano or aminocarbonyl;

R₈ represents alkyl or phenyl; and

M represents C—Cl, C—Br or N.

According to another aspect of the invention, Y may be a sugar moiety,preferably Y is a ring containing 4, 5, or 6 carbon atoms and which isinterrupted by one oxygen atom, the carbon atoms substituted by one ormore hydroxy groups, one or more CH₂OH groups or one or more OC(O)alkylgroups

The instant invention also provides arylpyrazoles of the followingformula (I bis):

wherein:

A is —NR₂₆—;

Y₁ is hydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, —S(O)_(a)R₂₈, —P(O)R₂₉R₃₀, —P(S)R₂₉R₃₀,—Si(R₃₁)(R₃₂)(R₃₃), —C(O)R₂₇, —C(S)R₂₇, cyano or nitro;

R₁₉ is hydrogen, alkyl, haloalkyl, or —NR₃₄R₃₅;

R₂₀ is —S(O)_(b)R₃₆ or R₃₇;

R₂₁ is hydrogen, halogen, —C(O)R₃₈, —S(O)_(c)R₃₉, alkyl, haloalkyl,—OR₄₀, —N═C(R₄₁)(R₄₂), alkenyl, —NR₄₃R₄₄, 1H-pyrrol-1-yl,1H-pyrazol-1-yl, or —CH═NOH;

R₂₂, R₂₃ and R₂₅ are independently selected from hydrogen, halogen oralkyl;

R₂₄ is halogen, haloalkyl, haloalkoxy, —S(O)_(d)R₄₅ or SF₅;

R₂₆ is hydrogen or substituted or unsubstituted alkyl;

R₂₇ is hydrogen, substituted or unsubstituted alkyl of C₁ to C₂₀,substituted or unsubstituted aryl, —OR₄₆, —NR₄₇R₄₈, or —SR₄₉;

R₂₈ is substituted or unsubstituted alkyl or substituted orunsubstituted aryl;

R₂₉ and R₃₀ are independently selected from alkoxy and thioalkoxy;

R₃₁, R₃₂ and R₃₃ are independently selected from alkyl, haloalkyl andaryl;

R₃₄ and R₃₅ are independently selected from hydrogen or substituted orunsubstituted alkyl;

R₃₆ is alkyl, alkenyl, alkynyl, or C₃-C₆ cycloalkyl each of which isoptionally substituted by one or more halogens;

R₃₇ is alkyl or haloalkyl;

R₃₈ is hydrogen, alkyl, haloalkyl, alkoxy or thioalkoxy;

R₃₉ is alkyl haloalkyl or aryl;

R₄₀ and R₄₁ are independently selected from hydrogen, alkyl andhaloalkyl;

R₄₂ is alkyl, haloalkyl, alkoxy or phenyl each of which is optionallysubstituted by one or more groups selected from hydroxy, halogen,alkoxy, —CN, alkyl, —S(O)_(e)alkyl;

R₄₃ and R₄₄ are independently selected from hydrogen, NH₂, —S(O)_(f)R₅₀,—C(O)R₅₁, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl and alkynyl; or R₄₃ and R₄₄ may form together adivalent alkylene radical which may be interrupted by one or moreheteroatoms, preferably selected from oxygen, nitrogen and sulfur;

R₄₅ is haloalkyl;

R₄₆ and R₄₉ are independently selected from substituted or unsubstitutedalkyl and substituted or unsubstituted aryl;

R₄₇ and R₄₈ are independently selected from hydrogen, substituted orunsubstituted alkyl and substituted or unsubstituted aryl; or R₄₇ andR₄₈ may form together a divalent alkylene radical which may beinterrupted by one or more heteroatoms preferably selected from oxygen,nitrogen and sulfur;

R₅₀ is substituted or unsubstituted alkyl;

R₅₁ is hydrogen, alkyl, haloalkyl, aryl, alkenyl, —OR₅₂, —SR₅₃, or—NR₅₄R₅₅;

R₅₂ and R₅₃ are independently selected from alkyl and haloalkyl;

R₅₄ and R₅₅ are independently selected from hydrogen, alkyl, haloalkyland aryl;

a, b, c, d, e and f independently represent zero, one or two;

M₁ is C-halo, C—CH₃, C—CH₂F, C—CH₂Cl, C—NO₂, or N;

or a pesticidally acceptable salt thereof.

A preferred group of compounds of formula (I bis) are those with one ormore of the following features wherein:

A is —NR₂₆—;

Y₁ is hydrogen, alkyl, or —C(O)R₂₇;

R₁₉ is hydrogen or NH₂;

R₂₀ is —S(O)_(b)R₃₆;

R₂₁ is —NR₄₃R₄₄;

R₂₂ is halogen;

R₂₃ and R₂₅ are hydrogen;

R₂₄ is haloalkyl;

R₂₇ is alkyl or O-alkyl; or

M is C-halo.

Another preferred group of compounds of formula (I bis) are thosewherein:

A is —NR₂₆—;

Y₁ is hydrogen, alkyl, or —C(O)R₂₇;

R₁₉ is hydrogen or NH₂;

R₂₀ is —S(O)_(b)R₃₆;

R₂₁ is —NR₄₃R₄₄;

R₂₂ is halogen;

R₂₃ and R₂₅ are hydrogen;

R₂₄ is haloalkyl;

R₂₇ is alkyl or O-alkyl; and

M is C-halo.

In the compounds of formula (I bis), preferably by the term“substituted” is meant by one or more of the following substituents:halogen, hydroxy, alkylthio, cyano, carboxy, —C(O)alkyl, —C(O)Oalkyl,—C(O)NH₂, —C(O)NHalkyl, —C(O)N(alkyl)₂, aryl, nitro, azido, amino,alkylamino, dialkylamino, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl,aryloxy, arylthio, alkylcarbonylamino, alkylcarbonyloxy, oraryloxycarbonyl.

Among the compounds of general formula (I) or (I bis) are the followingparticularly preferred compounds, which provide particularly usefulcontrol of insect species by systemic action. The compound numbers arefor reference purposes only.

1)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

2)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-ethylamino-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

3)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

4)5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

5)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

6)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehydeoxime

7)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-difluoromethylthio-1H-pyrazole-3-carboxaldehydeoxime

8)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehydeoxime

9)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehydeO-(methyl)oxime

10)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(acetyl)oxime

11)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(2-methylbenzoyl)oxime

12)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehlydeO-(methoxycarbonyl)oxime

13)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-[2-(ethoxycarbonyl)propionyl]oxime

14)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehydeO-(acetyl)oxime

15)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehydeO-(methoxycarbonyl)oxime

16)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-1H-pyrazole-3-carboxaldehydeoxime

17)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(methyl)oxime

18)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(N-methylcarbamoyl)oxime

19)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(carboxymethyl)oxime

20)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

21)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(tert-butyldimethylsilyl)oxime

22)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-formyl-N-hydroxy-4-trifluoromethylthio-1H-pyrazole-3-carboximidamide

23)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-hydroxyiminomethyl-4-trifluoromethylthio-1H-pyrazole-3-carboximidamide

24)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(isopropyl)oxime

25)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(ethoxycarbonylmethyl)oxime

26)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(aminocarbonylmethyl)oxime

27)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-[2-(ethylsulfonyl)ethyl]oxime

28)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(2-cyanoethyl)oxime

29)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carboxaldehydeoxime

30)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

31)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfonyl-1H-pyrazole-3-carboxaldehydeoxime

32)5-Amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

33)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio-5-methyl-1H-pyrazole-3-carboxaldehydeoxime

34)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-methyl-1H-pyrazole-3-carboxaldehydeoxime

35)1-[2-Chloro-4-(trifluoromethyl)phenyl]-5-[2-ethylsulfonyl(ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

36)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-dimethylamino-4-methylthio-1H-pyrazole-3-carboxaldehydeoxime

37)5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime

38)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H-pyrazole-3-carboxaldehydeoxime

39)3-Acetyl-5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazoleoxime

40)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidamide

41)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidamide

42)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfinyl-1H-pyrazole-3-carboximidamide

43)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylthio-1H-pyrazole-3-carboximidamide

44)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

45)5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

46)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfonyl-1H-pyrazole-3-carboximidamide

47)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylthio-1H-pyrazole-3-carboximidamide

48)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfonyl-1H-pyrazole-3-carboximidamide

49)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

50)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-N′-methyl-4-methylsulfinyl-1H-pyrazole-3-carboximidamide:

51)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-(2-fluoroethylsulfinyl)-1H-pyrazole-3-carboximidamide

52)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-(2-fluoroethylsulfonyl)-1H-pyrazole-3-carboximidamide

53)5-Amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-ethylsulfinyl-1-N-hydroxy-1H-pyrazole-3-carboximidamide

54)5-Amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide

55)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

56)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-ethylamino-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

57)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethysulfony)ethylamino]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

58)5-[2-(Cyano)ethylamino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

59)5-(Aminocarbonylmethylamino)-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

60)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-(phenylsulfonyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide

61)5-Amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-2-N-hydroxy-1H-pyrazole-3-carboximidamide

62)5-[2-Bromo-6-chloro-4-(trifluoromethyl)phenyl]-5-ethylamino-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide

63)5-Amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide

64)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-(methylsulfinyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide

65)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-(methylsulfinyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide

66)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-(ethylsulfinyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide

67)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[(prop-2-ynyl)amino]-N-hydroxy-1H-pyrazole-3-carboximidamide

68)5-Amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide.

Other compounds of formula (I) or (I bis) that are provided by theinstant invention include:

69)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-amino-1H-pyrazole-3-carboximidamide;

70)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(isopropylcarbonyl)amino-1H-pyrazole-3-carboximidamide;

71)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(n-heptylcarbonyl)amino-1H-pyrazole-3-carboximidamide;

72)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethoxycarbonyl)amino-1H-pyrazole-3-carboximidamide;

73)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-N-amino-1H-pyrazolecarboximidamide;

74)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-amino-1H-pyrazolecarboximidamide;

75)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-N-acetylamino-1H-pyrazolecarboximidamide;

76)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1-methylethenylcarbonylamino)-1H-pyrazolecarboximidamide;

77)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tert-butylcarbonylamino)-1H-pyrazolecarboximidamide;

78)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(2-methylethenylcarbonylamino)-1H-pyrazolecarboximidamide;

79)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethylcarbonylamino)-1H-pyrazolecarboximidamide;

80)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(propylcarbonylamino)-1H-pyrazolecarboximidamide;

81)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1-ethylpropylcarbonylamino)-1H-pyrazolecarboximidamide;

82)5-Amino-1-[2,6-dichloro-4-(trifluoronethyl)phenyl]-4-methylsulfinyl-N-(butylcarbonylamino)-1H-pyrazolecarboximidamide;

83)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(pentylcarbonylamino)-1H-pyrazolecarboximidamide;

84)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(hexylcarbonylamino)-1H-pyrazolecarboximidamide;

85)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-acetylamino-1H-pyrazolecarboximidamide;

86)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-chloroacetylamino-1H-pyrazolecarboximidamide;

87)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tridecylcarbonylamino)-1H-pyrazolecarboximidamide;

88)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(n-propoxycarbonylamino)-1H-pyrazolecarboximidamide;

89)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1,1-dimethylpropyloxycarbonylamino)-1H-pyrazolecarboximidamide;

90)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tertbutyloxycarbonylamino)-1H-pyrazolecarboximidamide;

91)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(acetyloxy)-1H-pyrazolecarboximidamide;

92)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-(acetyloxy)-1H-pyrazolecarboximidamide;

93)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethylcarbonyloxy)-1H-pyrazolecarboximidamide;

94)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(propylcarbonyloxy)-1H-pyrazolecarboximidamide;

95)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(2-methylethenylcarbonyloxy)-1H-pyrazolecarboximidamide;

96)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(benzoyloxy)-1H-pyrazolecarboximidamide;

97)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-N-(acetyloxy)-1H-pyrazolecarboximidamide;

98)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-N-(acetyloxy)-1H-pyrazolecarboximidamide;

99)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(heptylcarbonyloxy)-1H-pyrazolecarboximidamide;

100)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-N-(heptylcarbonyloxy)-1H-pyrazolecarboximidamide;

101)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-(acetyloxy)-1H-pyrazolecarboximidamide;

102)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-(heptylcarbonyloxy)-1H-pyrazolecarboximidamide;

103)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-N-(acetyloxy)-1H-pyrazolecarboximidamide;

104)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-formylamino-4-ethylsulfenyl-N-(acetyloxy)-1H-pyrazolecarboximidamide;

105)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(hexylcarbonyloxy)-1H-pyrazolecarboximidamide;

106)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(pentylcarbonyloxy)-1H-pyrazolecarboximidamide;

107)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(butylcarbonyloxy)-1H-pyrazolecarboximidamide;

108)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-(cyclopentylcarbonyloxy)-1H-pyrazolecarboximidamide;

109)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(cyclopentylcarbonyloxy)-1H-pyrazolecarboximidamide;

110)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tert-butylcarbonyloxy)-1-pyrazolecarboximidamide;

111)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(isopropylcarbonyloxy)-1H-pyrazolecarboximidamide;

112)1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-formylamino-4-ethylsulfinyl-N-(acetyloxy)-1H-pyrazolecarboximidamide;

113)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(chloroacetyloxy)-1H-pyrazolecarboximidamide;

114)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(bromoacetyloxy)-1H-pyrazolecarboximidamide;

115)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1-ethylpropylcarbonyloxy)-1H-pyrazolecarboximidamide;

116)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-[(3-acetyloxy)phenylcarbonyloxy]-1H-pyrazolecarboximidamide;

117)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfonyl-1H-pyrazole-3-carboximidamide;

118)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfenyl-1H-pyrazole-3-carboximidamide;

119)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-(methoxycarbonylamino)-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydehydrazone;

120)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-(methylsulfonylamino)-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydehydrazone;

121)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-amino-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehydehydrazone;

122)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-amino-4-trifluoromethylsulfenyl-1H-pyrazole-3-carboxaldehydehydrazone;

123)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-amino-4-methylsulfenyl-1H-pyrazole-3-carboximidamide;

124)5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-(furylcarbonylamino)-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;or

DETAILED DESCRIPTION OF THE INVENTION

Methods or Processes of Synthesis

The compounds of formula (I) can be prepared according to themanufacturing processes described in International Patent PublicationsNos. WO 94/21606 and WO 93/06089 or International Patent Publication No.WO 87/03781 as well as in European Patent Publication No. 0295117 andHatton et al U.S. Pat. No. 5,232,940. Those skilled in the art willchoose the proper initial reactant in these known methods and adaptthese known methods to the said reactant so as to obtain thecorresponding desired products. It is understood that in the descriptionof the following processes the sequences for the introduction of thevarious groups on the pyrazole ring may be performed in a differentorder and that suitable protecting groups may be required as will beapparent to those skilled in the art.

In the following description of processes when symbols appearing informulae are not specifically defined, it is to be understood that theyare “as defined above” in accordance with the first definition of eachsymbol in the specification.

According to a further feature of the present invention compounds ofgeneral formula (I) wherein R₂, R₃, R₄, R₅, M, X, Y and Z are as definedabove and R₁ represents amino (namely compounds of formula (Ia) or (Ib)in which R₁₅ represents hydrogen), may be prepared by the reaction of acompound of formula (II):

with a compound of formula (III):

NH₂OY

in which Y is defined above. The reaction is generally performed usingan acid salt of compound (III) for example the hydrochloride salt and inthe presence of a base for example pyridine or an alkali metal carbonate(such as sodium carbonate) or an alkali metal acetate (such as sodiumacetate) or ammonium acetate in a solvent such as methanol and/or waterat a temperature from 0° C. to 100° C.

According to a further feature of the present invention compounds ofgeneral formula (I) wherein R₂, R₃, R₄, R₅, M, X, Y and Z are as definedabove and R₁ represents amino may be prepared by the reaction of acompound of formula (IV):

wherein R represents alkyl, with a compound of formula (III) in which Ris alkyl and Y is defined above. The reaction is generally performedusing an using an acid salt of compound (III) for example thehydrochloride salt and optionally in the presence of a base for examplepyridine or an alkali metal carbonate (such as sodium carbonate) or analkali metal acetate (such as sodium acetate) or ammonium acetate in asolvent such as methanol and/or water at a temperature from 0° C. to100° C.

According to a further feature of the present invention compounds ofgeneral formula (I) wherein R₂, R₃, R₄, R₅, M, X, Y and Z are as definedabove and R₁ represents alkylamino or dialkylamino may be prepared bythe reaction of the corresponding compound of formula (I) wherein R₁represents amino with an alkylating agent preferably of formula R-halwhere R represent, alkyl and hal is chloro, bromo or iodo. The reactionis usually carried out in the presence of a strong base such aspotassium t-butoxide or sodium hydride in a solvent such astetrahydrofuran at a temperature from 0° C. to 100° C.

According to a further feature of the present invention compounds ofgeneral formula (I) wherein R₂, R₃, R₄, R₅, M, X, Y and Z are as definedabove and R₁ represents hydrogen or alkyl may be prepared by thereaction of a compound of formula (V):

in which R₁ represents hydrogen or alkyl with a compound of formula(III) in which Y is defined above and using the same conditions asemployed in the reaction of compounds of formula (II) with compounds offormula (III) above.

According to a further feature of the present invention compounds ofgeneral formula (I) wherein R₂, R₃, R₄, R₅, M, X and Z are as definedabove, R₁ represents hydrogen or alkyl, and Y is defined above with theexclusion of hydrogen, formyl, aryl, pyridinyl and pyrimidinyl (theexclusions being for chemical reasons only), may be prepared by reactionof the corresponding compound of formula (I) wherein Y representshydrogen with an appropriate alkylating or acylating reagent or Michaelacceptor generally in the presence of a base for example triethylaminein an inert solvent such as dichloroethane at a temperature of from 0°C. to 100° C.

According to a further feature of the present invention compounds ofgeneral formula (I) wherein Z represents R₁₂NH— or R₁₃R₁₄N— in whichR₁₂, R₁₃ and/or R₁₄ represent —C(O)alkyl optionally substituted by oneor more R₁₈ may be prepared by the acylation of the correspondingcompound wherein Z represents amino, according to methods described inone or more of International Publications No. WO 94/21606, WO 93/06089and WO 87/03781, European Patent Publication No. 0295117 and Hatton etal U.S. Pat. No. 5,232,940.

For the synthesis of 5-alkylamino and dialkylamino compounds wherein Zrepresents R₁₂NH— or R₁₃R₁₄N— in which R₁₂, R₁₃ and R₁₄ represent alkylor C-3 to C-6 alkenyl optionally substituted by R₁₈, including thecyclic amino compounds (i.e., the compounds in which R₁₃ and R₁₄ arejoined together) of formula (I), three basic methods are appropriate.The first method includes direct alkylation of precursor compounds offormula (I) in which Z represents amino with alkylating agents. Thesecond method involves a two-step sequence, with formation of the iminoethers, followed by a reduction. The third method of preparation isthrough a conjugate addition, e.g., a Michael-type addition.

The compounds of formula (I) wherein Z represents R₁₂NH— or R₁₃R₁₄N R₁₃in which R₁₂, R₁₃ and/or R₁₄ are R₇S(O)_(r), formyl, alkynyl,alkoxycarbonyl, alkylthiocarbonyl or aroyl, and R₇ and r are definedabove can be prepared by methods described in one or more ofInternational Publications No. WO 94/21606, WO 93/06089 and WO 87/03781,European Patent Publication No. 0295117 and Hatton et al U.S. Pat. No.5,232,940.

The compounds of formula (I) in which Z represents hydrogen, halogen,—S(O)_(n)R₈, —C(O)R₇, —C(O)OR₉, alkyl, haloalkyl, —N═C(R₁₀)(R₁₁),alkylthiocarbonyl and amino, R₁₂NH— or R₁₃R₁₄N— may be prepared bymethods described in one or more of International Publications NumbersWO 94/21606, WO 93/06089 and WO 87/03781, European Patent PublicationNumbers EP 0295117, EP 511845, EP 403309 and EP 403300, and Hatton et alU.S. Pat. No. 5,232,940, and German Patent Publication No. DE 19511269.

According to a further feature of the present invention compounds ofgeneral formula (I) wherein Z represents OR₉ may be prepared by methodsdescribed in U.S. Pat. Nos. 5,047,550 and 4,918,085.

According to a further feature of the present invention compounds offormula (I) in which the substituent Z is hydrazino, 1H-pyrrol-1-yl or1H-pyrazol-1-yl may be prepared according to the procedures described inEP 0352944. The synthesis of higher oxidation states of the compounds offormula (I), i.e., compounds in which m is 1 or 2, can be achieved byoxidation of the corresponding compounds in which m is 0 or 1.

Intermediates of formula (II) may be prepared by known methods (see forexample the above listed references).

Certain compounds of formula (II) are novel and as such constitute afurther feature of the invention.

Intermediates of formula (IV) wherein R represents alkyl may be preparedby the reaction of compounds of formula (II) with an alcohol of formulaROH where R is alkyl. The alcohol is usually employed in excess as thesolvent but a co-solvent such as tetrahydrofuran may be present. Thereaction is generally carried out in the presence of a base such assodium alkoxide at a temperature of from 0° C. to 100° C.

Intermediates of formula (V) wherein R₁ represents hydrogen or alkyl maybe prepared by known methods for example as described in WO 8703781 andEP 295117. For example where R₁ represents hydrogen by the reaction ofthe corresponding compound of formula (II) with diisobutylaluminiumhydride, and where R₁ represents alkyl by the reaction of thecorresponding compound of formula (II) with an organometallic reagent offormula R₁Q in which Q represents for example Mg-Cl or lithium in aninert solvent such as tetrahydrofuran.

Compounds of formula (IV) are novel and as such constitute a furtherfeature of the invention.

Certain compounds of formula (V) are novel and as such constitute afurther feature of the invention.

Intermediates of formula (III) are known or may be prepared by knownmethods.

According to a further feature of the present invention compounds ofgeneral formula (I bis) in which R₁₉ is amino may be prepared by thereaction of a compound of formula (II bis):

with a compound of formula (III bis):

H₂NNR₂₆Y₁  (III bis)

in which Y and A are defined above. The reaction is generally performedusing an acid salt of A compound of formula (III bis) for example thehydrochloride salt and in the presence of a base for example pyridine oran alkali metal carbonate (such as sodium carbonate) or an alkali metalacetate (such as sodium acetate) or ammonium acetate in a solvent suchas methanol and/or water at a temperature from 0° C. to 100° C.

According to a further feature of the present invention compounds ofgeneral formula (I bis) wherein R₁₉ is amino may be prepared by thereaction of a compound of formula (IV bis):

wherein R represents alkyl, with a compound of formula (III bis). Thereaction is generally performed using an using an acid salt of acompound of formula (III bis), for example the hydrochloride salt, andoptionally in the presence of a base (for example pyridine or an alkalimetal carbonate such as sodium carbonate) or an alkali metal acetate(such as sodium acetate or ammonium acetate) in a solvent such asmethanol and/or water and generally at a temperature from 0° C. to 100°C.

According to a further feature of the present invention compounds ofgeneral formula (I bis) wherein R₁₉ represents NR₃₄R₃₅ and wherein oneor both or of R₃₄ and R₃₅ are substituted or unsubstituted alkyl may beprepared by the reaction of the corresponding compound of formula (I)wherein R₁₉ represents amino with an alkylating agent formula R-halwhere R represents alkyl and hal is chloro, bromo or iodo, preferablyiodo. The reaction is usually carried out in the presence of a strongbase such as potassium t-butoxide or sodium hydride in a solvent such astetrahydrofuran at a temperature from 0° C. to 100° C.

According to a further feature of the present invention compounds ofgeneral formula (I bis) with the above definitions wherein R₁₉represents hydrogen or alkyl may be prepared by the reaction of acompound of formula (V bis):

in which R₁₉ represents hydrogen or alkyl with a compound of formula(III bis) defined above and using the same conditions as employed in thereaction of compounds of formula (II bis) with compounds of formula (IIIbis) above.

According to a further feature of the invention, compounds of formula (Ibis) wherein Y is —S(O)_(a′)R₂₈, —P(O)R₂₉R₃₁, —P(S)R₂₉R₃₀,—Si(R₃₁)(R₃₂)(R₃₃), —C(O)R₂₇, —C(S)R₂₇, cyano or nitro may be preparedby reaction of a compound of formula (I bis) wherein Y₁ is hydrogen,with sulfenylating, sulfinylating, sulfonating phosphorylating,thiophosphorylating, silylating, acylating or thioacylating reagent,respectively, generally in the presence of a base such as triethylamineor sodium carbonate and generally in a solvent at a temperaturegenerally in the range −100 to 100° C.

According to a further feature of the invention for the synthesis of5-alkylamino and dialkylamino compounds of formula (I bis) wherein R₂₁represents R₄₃NH— or R₄₃R₄₄N— in which R₄₃ and R₄₄ represent substitutedor unsubstituted alkyl or substituted or unsubstituted C-3 or C-6alkenyl three basic methods are appropriate. The first method includesdirect alkylation of precursor compounds of formula (I bis) in which R₂₁represents amino with alkylating agents. The second method involves atwo-step sequence, with formation of the imino ethers, followed by areduction. The third method of preparation is through a conjugateaddition, e.g., a Michael-type addition.

The compounds of formula (II bis) wherein R₂, R₃, R₄, R₅, R₆ and M arethe above described substituents can be prepared by methods described inone or more of the following: WO 94/21606, WO 93/06089, WO 87/03781, WO97/22593; European Patent Publications EP 0295117, EP 0511845, EP0403309, EP 0403300, EP 352944, EP 780378; U.S. Pat. Nos. 5,232,940,5,047,550, 4,918,085; German Patent Publication No. 19511269; or bymethods known to the skilled in the art.

The synthesis of higher oxidation states of the compounds of formula (Ibis), i.e., compounds in which a, b, c, d, e or f are 1 or 2, can beachieved by oxidation of the corresponding compounds in which thosevariable are is 0 or 1.

Intermediates of formula (II bis) may be prepared by known methods (seefor example the above listed references).

REPRESENTATIVE COMPOUNDS OF THE INVENTION

The compounds of TABLE 1 are illustrative of some of the preferredcompounds of general formula (I) wherein R₃ and R₅ represent hydrogenand can be prepared by the herein described methods or processes ofsynthesis, by the appropriate selection of reactants, conditions andprocedures, which are commonly known and apparent to one skilled in theart. In Table 1 Me means methyl, Et means ethyl and where subscripts areomitted they should be present, for example CH2 means CH₂.

TABLE 1 Cmpd No. M Z R₁ R₂ R₄ X Y 126 C—Cl NH(CH₂)₂SO₂Me NH₂ Cl CF₃SOCH₃ H 127 C—Cl NHCH₂CN NH₂ Cl CF₃ SOCH₃ H 128 C—Cl NH(CH₂)₂CONH₂ NH₂Cl CF₃ SOCH₃ H 129 C—Cl NHMe NH₂ Cl CF₃ SOMe Me 130 C—Cl NHEt NH₂ Cl CF₃SOMe Me 131 C—Cl EtSO₂(CH₂)₂NH NH₂ Cl CF₃ SOMe Me 132 C—Cl NH(CH₂)₂CNNH₂ Cl CF₃ SOMe Me 133 C—Cl NHCH₂CONH₂ NH₂ Cl CF₃ SOMe Me 134 C—Cl NHMeNH₂ Cl CF₃ SMe Me 135 C—Cl NHEt NH₂ Cl CF₃ SMe Me 136 C—Cl EtSO₂(CH₂)₂NHNH₂ Cl CF₃ SMe Me 137 C—Cl NH(CH₂)₂CN NH₂ Cl CF₃ SMe Me 138 C—ClNHCH₂CONH₂ NH₂ Cl CF₃ SMe Me 139 C—Br NHMe NH₂ Cl CF₃ SOMe H 140 C—BrEtSO₂(CH₂)₂NH NH₂ Cl CF₃ SOMe H 141 C—Br NH(CH₂)₂CN NH₂ Cl CF₃ SOMe H142 C—Br NHCH₂CONH₂ NH₂ Cl CF₃ SOMe H 143 C—Cl NHMe NH₂ Cl CF₃O SOMe H144 C—Cl NHEt NH₂ Cl CF₃O SOMe H 145 C—Cl EtSO₂(CH₂)₂NH NH₂ Cl CF₃O SOMeH 146 C—Cl NH(CH₂)₂CN NH₂ Cl CF₃O SOMe H 147 C—Cl NHCH₂CONH₂ NH₂ Cl CF₃OSOMe H 148 C—Cl NHMe NH₂ Cl CF₃O SOMe Me 149 C—Cl NHEt NH₂ Cl CF₃O SOMeMe 150 C—Cl EtSO₂(CH₂)₂NH NH₂ Cl CF₃O SOMe Me 151 C—Cl NH(CH₂)₂CN NH₂ ClCF₃O SOMe Me 152 C—Cl NHCH₂CONH₂ NH₂ Cl CF₃O SOMe Me 153 C—Cl NH₂ NH₂ ClCF₃ SOMe CH₂CO₂Et 154 C—Cl NHMe NH₂ Cl CF₃ SOMe CH₂CO₂Et 155 C—Cl NHEtNH₂ Cl CF₃ SOMe CH₂CO₂Et 156 C—Cl EtSO₂(CH₂)₂NH NH₂ Cl CF₃ SOMe CH₂CO₂Et157 C—Cl NH(CH₂)₂CN NH₂ Cl CF₃ SOMe CH₂CO₂Et 158 C—Cl NHCH₂CONH₂ NH₂ ClCF₃ SOMe CH₂CO₂Et 159 C—Cl NH₂ NH₂ Cl CF₃ SOMe CH₂CONH₂ 160 C—Cl NHMeNH₂ Cl CF₃ SOMe CH₂CONH₂ 161 C—Cl NHEt NH₂ Cl CF₃ SOMe CH₂CONH₂ 162 C—ClEtSO₂(CH₂)₂NH NH₂ Cl CF₃ SOMe CH₂CONH₂ 163 C—Cl NH(CH₂)₂CN NH₂ Cl CF₃SOMe CH₂CONH₂ 164 C—Cl NHCH₂CONH₂ NH₂ Cl CF₃ SOMe CH₂CONH₂ 165 C—Cl NHMeNHMe Cl CF₃ SOMe Me 166 C—Cl NHEt NHMe Cl CF₃ SOMe Me 167 C—ClEtSO₂(CH₂)₂NH NHMe Cl CF₃ SOMe Me 168 C—Cl NH(CH₂)₂CN NHMe Cl CF₃ SOMeMe 169 C—Cl NHCH₂CONH₂ NHMe Cl CF₃ SOMe Me 170 C—Cl NH₂ NHEt Cl CF₃ SOMeMe 171 C—Cl NHMe NHEt Cl CF₃ SOMe Me 172 C—Cl NHEt NHEt Cl CF₃ SOMe Me173 C—Cl EtSO₂(CH₂)₂NH NHEt Cl CF₃ SOMe Me 174 C—Cl NH(CH₂)₂CN NHEt ClCF₃ SOMe Me 175 C—Cl NHCH₂CONH₂ NHEt Cl CF₃ SOMe Me 176 C—Cl NH₂ NHMe ClCF₃ SOMe CH₂CO₂Me 177 C—Cl NHMe NHMe Cl CF₃ SOMe CH₂CO₂Me 178 C—Cl NHEtNHMe Cl CF₃ SOMe CH₂CO₂Me 179 C—Cl EtSO₂(CH₂)₂NH NHMe Cl CF₃ SOMeCH₂CO₂Me 180 C—Cl NH(CH₂)₂CN NHMe Cl CF₃ SOMe CH₂CO₂Me 181 C—ClNHCH₂CONH₂ NHMe Cl CF₃ SOMe CH₂CO₂Me

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Detailed Examples of Compound Synthesis

The following EXAMPLES 1 to 17 and REFERENCE EXAMPLES 1 to 24 illustratedetailed methods of synthesis and the physical properties ofrepresentative pesticidal compounds of formula (I) (and their chemicalintermediates) according to the invention. These example compounds andothers prepared in a similar manner, following the detailed proceduresor other methods or processes herein described, are shown in Tables 2.Additionally, one or more spectroscopic analyses (IR, H¹ or F¹⁹ NMR, MS,etc.) have been performed on each compound for characterization andconfirmation of the chemical structure. In the following Tables Me meansmethyl, Et means ethyl, 2-Tolyl means 2-methylphenyl and C₂H meansethynyl.

Example 1

A mixture of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde(2.74 g), hydroxylamine hydrochloride (0.99 g) and pyridine (1.68 g) wasstirred in methanol at 46° C. for 2.8 hours, evaporated, washed (water)and crystallized from ethanol to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (1.74 g) as a white solid m.p.219-221° C. (decomposition).Compound 1

In a manner similar to that employed above, the following compoundsshown in Table 2 were also prepared.

TABLE 2

Cmpd No. # M Y R₁ R₂ R₄ X Z M.p. ° C. 35 C—Cl H H H CF₃ SOMeNH(CH₂)₂SO₂Et   157-157.5 36 C—Cl H H Cl CF₃ SMe NMe₂ 178-181 37 C—Cl HH Cl OCF₃ SOEt NH₂ 204-206 38 C—Cl H H Cl CF₃ CF₃ NH₂ 136-146 39 C—Cl HMe Cl CF₃ SOMe NH₂ 68-71  2 C—Cl H H Cl CF₃ SOMe NHEt 158-161  3 C—Cl HH Cl CF₃ SOMe NHMe 162  4 C—Cl H H Cl OCF₃ SOMe NH₂ 144-146  5 C—Cl H HCl CF₃ SOEt NH₂ 195  6 C—Cl H H Cl CF₃ SCF₃ NH₂ 163-169  7 C—Cl H H ClCF₃ SCHF₂ NH₂ 146-152  8 C—Cl H H Cl CF₃ SMe NH₂ 179-181 29 C—Cl H H ClCF₃ SMe Me   160-162.5 32 N H H Cl CF₃ SOMe NH₂ 195.5-196.5 33 C—Cl H HCl CF₃ SEt Me 155-157 34 C—Cl H H Cl CF₃ SOEt Me 210-213

Example 2

A mixture of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehyde(0.66 g), methoxyamine hydrochloride (0.2 g) and pyridine was stirred atroom temperature for 26 hours. Pyridine was evaporated and the residuedissolved in ethyl acetate/acetonitrile, washed with 1% aqueous HCl,dried (MgSO₄) and evaporated. The residue was purified by silica gelcolumn chromatography, eluting with hexane/ethyl acetate, to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehydeO-methyloxime (0.3 g) as a white solid m.p. 129-131.5° C. Compound 9.

Example 3

Acetyl chloride (0.27 ml) was added to a solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (1.0 g) and triethylamine (0.56 ml) in tetrahydrofuran at 0° C.and the mixture stirred for 1 hour. The solvent was evaporated and theresidue chromatographed on silica gel eluting with 3:1dichloromethane/ethyl acetate to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(acetyl)oxime (0.83 g)as an orange solid m.p.130-134° C. Compound 10.

In a manner similar to that employed above the following compounds shownin Table 3 were also prepared.

TABLE 3 Cmpd No. M.p.° C. 11 107-110 12 165 13 52-54 14 205.5-206.5 15171-173 91 156 92 205 93 112 94 149 95 192 96 194 97 127 98 127 99 112100 oil 101 oil 102 113 103 190 104 167 105 107

Example 4

A mixture of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-mehtylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (1.38 g), 30% hydrogen peroxide (1.38 ml) sodium tungstatedihydrate (0.17 g) in methanol/acetic acid was stirred at 20° C.overnight, then at 50° C. for 4 hours, and again at 20° C. overnight.Water was added and the solid filtered, water-washed and dried to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-1H-pyrazole-3-carboxaldehydeoxime (0.93 g) m.p.209.5-211° C. (decomposition). Compound 16.

Example 5

A solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)-phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (0.15 g) in ethanol was added to a solution of sodium ethoxide(0.025 g) in ethanol at 20° C., followed by iodomethane (0.023 ml). Thereaction was monitored by HPLC and over the next 24 hours threeadditional equivalents of iodomethane were added. The reaction mixturewas then, concentrated and partitioned between dichloromethane andwater. The organic layer was water-washed, dried (MgSO₄) andconcentrated. This was then combined with crude product from anotheridentical preparation and chromatographed on a silica gel column,eluting with hexane/ethyl acetate, to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(methyl)oxime (0.06 g) as a yellow solid m.p.80° C. Compound 17.

Example 6

A mixture of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (1.5 g), methyl isocyanate (0.705 g), and dibutyltin diacetate (2drops) was stirred in dichloromethane at 20° C. in a sealed bottle for 2days. The mixture was partitioned between water and dichloromethane, theorganic layer dried (Na₂SO₄) and evaporated and the residue crystallizedfrom ethyl acetate/hexane to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(N-methylcarbamoyl)oxime (1.22 g) m.p.146-147° C. Compound 18.

Example 7

A mixture of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde(5.15 g) and carboxymethoxylamine hemihydrochloride (5.83 g) was stirredat 20° C. in pyridine/methanol for 17 hours. The methanol was evaporatedand the residue water-washed and subjected to flash columnchromatography on silica gel, eluting with acetic acid/ethyl acetate(1:9) to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(carboxymethyl)oxime (1.44 g). Mass spectrometric analysis of theproduct indicated a molecular weight of 458. Compound 19.

Example 8

Tert-butyl nitrite (1.25 g) was added to5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (2.0 g) in tetrahydrofuran and stirred for 4.5 hours. Afterevaporation the resulting orange solid was triturated with carbontetrachloride to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (0.24 g) m.p.239-240° C. Compound 20.

Example 9

A solution of tert-butyldimethylsilyl chloride (0.8 g) inN,N-dimethylformamide (DMF) was added to a stirred solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (2.0 g) in (DMF), followed by dropwise addition of a solution ofimidazole (0.72 g) in DMF during 7-minutes. The mixture was heated at50° C. for 3.5-hours and then held at 20° C. for 18 hours. The mixturewas diluted (water), extracted (methyl tert-butyl ether) and the organicphase washed in turn with NaHCO₃ solution, 5% HCl solution and withNaHCO₃ solution, dried (MgSO₄), filtered and evaporated. The residue waspurified by flash chromatography on silica gel to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(tert-butyldimethylsilyl)oxime (0.76 g)as a light yellow solidm.p.150-154° C. Compound 21.

Example 10

To a stirred solution of1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-formyl-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile(3.0 g) in ethanol was added a solution of hydroxylamine hydrochloride(0.46 g) and sodium carbonate (0.9 g) in water. After 1 hour the mixturewas poured into water, extracted (ethyl ether), dried (sodium sulfate)and evaporated. Purification by column chromatography on silica gel gave1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-formyl-N-hydroxy-4-trifluoromethylthio-1H-pyrazole-3-carboximidamide(0.255 g), m.p.72-75° C. Compound 22.

The following compounds shown in Table 4 were prepared in a similarmanner.

TABLE 4

Cmpd No. # M Z R R₂ R₄ Y X M.p. ° C. 42 C—Cl NH₂ H Cl CF₃ H SOEt 186-18943 C—Cl NH₂ H Cl CF₃ H SEt 170-175 44 C—Cl NH₂ H Cl CF₃ H SOMe 225-22745 C—Cl NH₂ H Cl CF₃O H SOMe 198-200 46 C—Cl NH₂ H Cl CF₃ H SO₂Me109-111 47 C—Cl NH₂ H Cl CF₃ H SMe 207-208 48 C—Cl NH₂ H Cl CF₃ H SO₂Et109-111 51 C—Cl NH₂ H Cl CF₃ H SOCH₂CH₂F 212-215 52 C—Cl NH₂ H Cl CF₃ HSO₂CH₂CH₂F 107-111 53 N NH₂ H Cl CF₃ H SOEt 164-168 54 N NH₂ H Cl CF₃ HSOMe 234-235 55 C—Cl NHMe H Cl CF₃ H SOMe 191-192 56 C—Cl NHEt H Cl CF₃H SOMe 192-193 57 C—Cl NH(CH₂)₂SO₂Et H Cl CF₃ H SOMe 150-152 58 C—ClNH(CH₂)₂CN H Cl CF₃ H SOMe 175-176 59 C—Cl NHCH₂CONH₂ H Cl CF₃ H SOMe119-120 60 C—Cl NH(CH₂)₂SO₂Ph H Cl CF₃ H SOMe 131-134 61 C—Br NH₂ H BrCF₃ H SOMe 240-241 62 C—Br NHEt H Cl CF₃ H SOMe 213-214 63 C—Br NH₂ H ClCF₃ H SOMe 237-238 64 C—Cl NH(CH₂)₂SOMe H Cl CF₃ H SOEt 108-109 65 C—ClNH(CH₂)₂SOMe H Cl CF₃ H SOMe 150-151 66 C—Cl NH(CH₂)₂SOEt H Cl CF₃ HSOEt 173-175 67 C—Cl NHCH₂C₂H H Cl CF₃ H SOMe 194-196 68 C—Cl NH₂ H HCF₃ H SOMe 238-239

Example 11

A mixture of1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-formyl-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile(1.0 g), hydroxylamine hydrochloride (0.48 g) and sodium acetatetrihydrate (0.94 g) in ethanol was heated under reflux for one hour.After cooling to 20° C. the mixture was concentrated and partitionedbetween water and ether. The organic phase was washed (brine), dried(magnesium sulfate) and evaporated to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-hydroxyiminomethyl-4-trifluoromethylthio-1H-pyrazole-3-carboximidamide(0.5 g), m.p.68-72° C. Compound 23.

Example 12

A suspension of sodium ethoxide (0.34 g) in ethanol was added to astirred solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (2.0 g) in ethanol. 2-Iodopropane (1 ml) was then added and themixture stirred overnight at 20° C. and evaporated. The residue (indichloromethane) was water-washed, dried (magnesium sulfate),concentrated and purified by chromatography on silica gel to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(isopropyl)oxime (0.35 g), m.p.128-130° C. Compound 24.

By proceeding in a similar manner the following compounds were alsoprepared:

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1-H-pyrazole-3-carboxaldehydeO-(ethoxycarbonylmethyl)oxime, Compound 25, m.p.127-128° C.; and

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1-H-pyrazole-3-carboxaldehydeO-(carbamoylmethyl)oxime, Compound 26, m.p.165-167° C.

Example 13

In a manner similar to that employed in Example 12 an ethanol solutionof5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime was reacted with sodium ethoxide and ethyl vinyl sulfone to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-[2-(ethylsulfinyl)ethyl]oxime, m.p.144-148° C. Compound 27.

Example 14

In a manner similar to that employed in Example 12 an ethanol solutionof5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime was reacted with sodium ethoxide and acrylonitrile to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(2-cyanoethyl)oxime. Compound 28, as the 85 percent (by weight)component of a mixture containing 8 percent of the oxime startingmaterial. Mass spectrometric analysis of the product indicated thefollowing: MS m/e=453 (M⁺).

Example 15

30% Hydrogen peroxide solution (0.32 ml) was added to a solution of1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carboxaldehydeoxime (0.8 g) in trifluoroacetic acid at 20° C. The reaction solutionwas partitioned between water and dichloromethane and the organic layerdried (magnesium sulfate), evaporated and flash-chromatographed onsilica gel, eluting with dichloromethane/ethyl acetate (3:1) to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (0.29 g), m.p.210-214° C. Compound 30 and1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfonyl-1H-pyrazole-3-carboxaldehydeoxime (0.2 g), m.p.211-212° C. Compound 31.

Example 16

To a stirred solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboximidicacid methyl ester (1.0 g) in anhydrous methanol was added anhydrousmethoxylamine hydrochloride (0.2 g). After 4 hours at 20° C., themixture was evaporated and dichloromethane and water added. The organiclayer was dried (MgSO₄), evaporated and chromatographed on a florisilcolumn, eluting with 3:1 dichloromethane/ethyl acetate to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide(0.28g), m.p.140-145° C. Compound 49. By proceeding in a similar manner thefollowing compounds were prepared:5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidamide,m.p.169-170° C. Compound 41; and5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidamide,m.p.222-224° C. Compound 40.

Example 17

A solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide(0.5 g) in anhydrous THF was stirred at 0-5° C. and potassiumtert-butoxide (0.13 g) and iodomethane (0.081 ml) added. After threehours further potassium tert-butoxide (0.068 g) and iodomethane (0.08ml) were added at 0-5° C. The mixture was stirred at this temperaturefor 16 hours, evaporated and the residue purified by chromatography onsilica gel eluting with 3:1 dichloromethane/ethyl acetate to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-N′-methyl-4-methylsulfinyl-1H-pyrazole-3-carboximidamide(0.13 g), m.p. 139-142° C. Compound 50.

Example 18

A mixture of5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole(550 g), anhydrous hydrazine (700 g) in absolute ethanol (1.55 L) wasstirred at ambient temperature for four hours. Water (6.5 L) was addedand the precipitate filtered and washed with water. After 12 hoursanother batch of precipitate was filtered. All solids were combined toprovide 568 g of Compound 69 as a white solid, m.p. 210° C.

In a similar manner the following compounds were prepared:

Compound 73 m.p. 170° C.;

Compound 74 m.p. 193° C.

Example 19

The mixture of Compound 69 (1.0 g) and acetic anhydride(327 mg) inp-dioxane (10 ml) was stirred at room temperature for 2 days. Themixture was evaporated and the residue washed with hexane with smallamount of ethyl acetate and the suspension filtered to give 1.08 g ofCompound 75, m.p 230° C.

Compound 85 was synthesized using a similar procedure.

Example 20

The mixture of Compound 69 (0.2 g) and propionic anhydride (0.07 ml) intetrahydrofuran (5 ml) was stirred at room temperature for 6 days. Themixture was evaporated and the residue purified by silica gelchromatography to give 70 mg of Compound 79, m.p. 155-162° C.

In a similar manner the following compounds were prepared:

Compound # m.p. 76 95 77 160 70 118 78 160 79 155 80 160 81 110 82 11883 152 84 130 71 122 86 oil

Example 21

The mixture of Compound 69 (0.2 g) and di-t-amyldicarbonate (0.13 ml) intetrahydrofuran (4.5 ml) was stirred at room temperature for 5 days. Themixture was evaporated and the residue purified by silica gelchromatography to give 20 mg (0.038 mmol) of Compound 89, m.p. 95-98° C.

The following compounds were synthesized with the similar procedureusing an appropriate dicarbonates: Compound 88, m.p. 135° C., Compound90, m.p. 155° C., Compound 72, m.p. 196° C.

Example 22

To a suspension of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulfinylpyrazole(20 g) in methanol (120 ml) was added hydroxylamine hydrochloride (3.99g), followed by addition of triethylamine (8.0 ml). The mixture wasstirred at room temperature overnight then evaporated. The residue waspartitioned between water and ethyl acetate. The organic layer waswashed with water, followed by wash with brine. The organic layer wasdried over anhydrous sodium sulfate. The solution was concentrated byevaporation of solvent. A precipitate was formed and collected byfiltration. The solid was washed with small amount of ethyl acetate togive Compound 44 (16.1 g), m.p. 225-226° C.

Reference Example 1

Diisobutylaluminum hydride (1M in toluene, 391 ml) was added dropwiseduring 1.5 hours to5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-3-carbonitrile(50 g) in dry THF at −20° C. The partially evaporated mixture was thenquenched by addition to acetonitrile/water at 0-50° C. Aluminum saltswere filtered, the filtrate evaporated and the residue extracted withdichloromethane. The extract was dried (MgSO₄), and evaporated to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde(47.1 g).

By proceeding in a similar manner the following compounds shown in Table5 were also prepared.

TABLE 5

HPLC Reten- tion Time^((a)) M R₂ R₄ X Z (Min.) C—Cl Cl CF₃ SOMe NHEt3.76 C—Cl Cl CF₃ SOMe NHMe 3.49 C—Cl Cl CF₃ SOEt NH₂ (M.p. 166-168° C.)C—Cl Cl CF₃ SMe NH₂ 4.04 C—Cl Cl CF₃O SOMe NH₂ 3.41 C—Cl Cl CF₃ SMe Me7.64 N Cl CF₃ SOMe NH₂ 3.04 C—Cl Cl CF₃ SEt Me 8.22 C—Cl Cl CF₃ SMe NMe₂10.08 C—Cl Cl CF₃ SCF₃ NH₂ 4.83 C—Cl Cl CF₃ CF₃ NH₂ ^((b)) C—Cl H CF₃SOMe NH(CH₂)₂SO₂Et ^((b)) C—Cl Cl CF₃O SOEt NH₂ ^((b)) C—Cl Cl CF₃ SCHF₂NH₂ ^((b)) C—Cl Cl CF₃ SOEt NH₂ ^((b)) ^((a))25.0 cm × 4.6 mm SUPELCOSILLC-18 Column. Eluant: MeCN/H₂O (3:1) at one ml/minute. ^((b))usedwithout purification in the next stage

Reference Example 2

A 1.4 M solution of methyllithium (31 ml) in ethyl ether was added to astirred solution of5-bromo-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile(17.67 g) in dry tetrahydrofuran (THF) at −65° C. over 15-minutes andallowed to warm to 0° C. over 3-hours. After recooling to −65° C.,methyl iodide (3.06 ml) in THF was added over 3 minutes, the mixturewarmed to −20° C. over 1.5 hours, and then partitioned between aqueousammonium chloride and dichloromethane. The organic phase was dried(magnesium sulfate), evaporated and purified by flash chromatography onsilica gel eluting with hexane/methyl tert-butylether to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carbonitrile(6.2 g) having a purity of 90.7 area percent by HPLC.

By proceeding in a similar manner the following compound was alsoprepared:1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio-5-methyl-1-H-pyrazole-3-carbonitrilem.p.79-82° C.

Reference Example 3

30% Hydrogen peroxide (1.82 ml) was added to a stirred solution of1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carbonitrile(6.2 g) in methanol, containing i-PrOH/H₂SO₄ catalyst (5.31 ml)described by Drabowicz, et al (above) at 0-5° C. The mixture was allowedto warm to 20° C. over 17 hours. Additional hydrogen peroxide (5.46 ml)was added in three portions over the next 24 hours, along with thecatalyst (5 ml). After stirring for a further 60 hours water was addedto give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfinyl-1H-pyrazole-3-carbonitrile(6.72 g) as a yellow oil (91.7% area purity by HPLC) having a retentiontime of 3.61 minutes on a 25.0 centimeter by 4.6 millimeter SUPELCOSILLC-18 column, eluting with CH₃CN/H₂O (3:1) solvent at 1 ml/minute.

By proceeding in a similar manner the following compounds were alsoobtained:

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-methyl-1-H-pyrazole-3-carbonitrile,m.p.109-115° C.;

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)sulfinyl]-1-H-pyrazole-3-carbonitrile,m.p.182-183° C.;

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylsulfinyl)ethylamino]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.106-108° C., from1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylthio)ethylamino]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile;

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylsulfinyl)ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.114-116° C. from1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylthio)ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile;

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfinyl)ethylamino]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.138-140° C. from1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylthio)ethylamino]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile;

5-amino-1-[3-chloro-5-(trifluoromethyl)pyrid-2-yl]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.150-152° C.; and

5-amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.165-166° C.

Reference Example 4

90% Tertiary-butyl nitrite (27.9 ml) was slowly added to a stirredsolution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio-1H-pyrazole-3-carbonitrile(49.8 g) in bromoform (600 ml) at 0-5° C. The mixture was stirred forthree hours whilst warming to 20° C. evaporated and re-evaporated afteraddition of hexane/ethyl acetate (1:1) to give5-bromo-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio-1H-pyrazole-3-carbonitrile(32.65 g), showing 93.3 area % purity by HPLC and with a retention timeof 11.26 minutes on a 25.0 cm by 4.6 mm SUPELCOSIL LC-18 column, elutingwith CH₃CN/H₂O (3:1) solvent at 1 ml/minute. By proceeding in a similarmanner the following compound was prepared:5-bromo-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile,m.p.134-140° C.

Reference Example 5

Ozone was bubbled through a solution of1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(E-2-methoxycarbonylethenyl)-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile(36.6 g) in dichloromethane at −78° C. for 3 hours. The intensely bluesolution was decolorized with oxygen gas, then treated withdimethylsulfide (19 ml) and allowed to warm to 20° C. during 14 hoursThe mixture was then washed with water, dried (magnesium sulfate),filtered and evaporated to give1-(2,6-dichloro-4-trifluoromethylphenyl)-5-formyl-4-trifluoromethylthio-1H-pyrazole-3-carbonitrileas white crystals (30.7 g), m.p.90° C.

Reference Example 6

1,8-Diazabicyclo-[5,4,0]-undec-7-ene (13 ml) was added to a solution of5-(2′-bromo-2′-carbomethoxy)ethyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile(45 g) in toluene and stirred for 0.5 hour. The mixture was diluted(ethyl acetate), and washed with water, hydrochloric acid solution,saturated sodium hydrogen carbonate solution and brine. The organicphase was dried (magnesium sulfate), concentrated and triturated withcold pentane to give1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(E-2-methoxycarbonylethenyl)-4-trifluoromethylthio-1H-pyrazole-3-carbonitrileas a white solid (36.6 g), m.p.90° C.

Reference Example 7

A solution of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile(100 g) in acetonitrile was added dropwise to a mixture of methylacrylate (430 ml), copper (II) bromide (80 g) and 90% tert-butylnitrite(51 ml) in acetonitrile at 0° C., warmed to 20° C. and stirred for 12hours. The mixture was diluted (ether), washed (water), dried (magnesiumsulfate) and concentrated. Trituration with hexane gave5-(2′-bromo-2′-carbomethoxy)ethyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthio-1H-pyrazole-3-carbonitrileas a white solid (72.7 g) m.p.122° C.

Reference Example 8

To a stirred suspension of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile(5.0 g) in anhydrous methanol was added a 25% w/w solution of sodiummethoxide (8.95 ml) in methanol, at 20° C. The mixture was stirred for16-hours, cooled to 0° C. and diluted with ice-cold anhydrous methanol.Carbon dioxide was passed into the solution for 15-minutes until a pH of8 was attained. The precipitate was filtered off, washed (ethyl acetate)and evaporated to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboximidicacid methyl ester (3.65 g), ¹H NMR (CDCl₃) in ppm: 8.34 (s, 1H), 7.79(s, 2H), 5.11 (brs, 2H), 3.93 (s, 3H), 2.94 (s, 3H). By proceeding in asimilar manner the following compound was prepared:5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidicacid methyl ester, m.p.179-180° C.

Reference Example 9

To a stirred solution of4,4′-dithiobis[5-amino-3-cyano-1-{2,6-dichloro-4-(trifluoromethyl)phenyl}-1H-pyrazole(1.0 g) in methanol was added sodium borohydride (0.03 g). After7-minutes 1-bromo-2-fluoroethane (0.05 ml) was added. Five furtherportions of sodium borohydride (0.15 g) and 1-bromo-2-fluoroethane (0.25ml) were added over 5 hours. The mixture was evaporated, dichloromethaneand water added and the organic phase dried (MgSO₄) and re-evaporated togive5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)thio]-1H-pyrazole-3-carbonitrile(1.09 g), m.p.130-131.5° C. By proceeding in a similar manner thefollowing compound was obtained:

5-amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-ethylthio-1H-pyrazole-3-carbonitrile,m.p.127-128° C.4,4′-Dithiobis[5-amino-3-cyano-1-{2,6-dichloro-4-(trifluoromethoxy)phenyl}-1H-pyrazoleused above may be prepared in a similar manner to4,4′-dithiobis[5-amino-3-cyano-1-{2,6-dichloro-4-(trifluoromethyl)phenyl}-1H-pyrazoleas described in French Patent Application numbers 8816710 and 8913371.

Reference Example 10

In a manner similar to that of Example 15,5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)thio]-1H-pyrazole-3-carbonitrilewas oxidized with hydrogen peroxide in trifluoroacetic acid solution togive5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)sulfonyl]-1H-pyrazole-3-carbonitrile,m.p.192-193° C. By proceeding in a similar manner the followingcompounds were prepared:

5-amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.150-151° C.5-amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.137-138° C.5-amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.146-147° C.

Reference Example 11

A mixture of1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-amino-1H-pyrazole-3-carbonitrile(5.0 g), trimethyl orthoacetate (100 ml) and p-toluenesulfonic acid (0.2g) in toluene was heated to 145° C. for 2 hours and then at 130° C. withdistillation of the methanol. The mixture was evaporated and the residuepurified by column chromatography using 20% ethyl acetate in hexane togive1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[1-(methoxyethylene)amino]-1H-pyrazole-3-carbonitrile(3.31 g) m.p.164 to 165° C.

Reference Example 12

To a suspension of1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[1-(methoxyethylene)amino]-1H-pyrazole-3-carbonitrile(6.0 g) in methanol was added sodium borohydride (0.79 g) in threeportions over 15 min. at 20° C. then stirred under nitrogen for 45 mins.After evaporation the residue was purified by column chromatography onsilica gel using 15% ethyl acetate in methylene chloride to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-ethylamino-1H-pyrazole-3-carbonitrile(1.1 g), m.p.130-131° C. (decomp.).

By proceeding in a similar manner was prepared:

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.147-150° C. (decomposition).

By proceeding in a similar manner but replacing sodium borohydride withsodium cyanoborohydride was prepared:

1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-ethylamino-1H-pyrazole-3-carbonitrile,m.p.125-126.5° C.

Reference Example 13

A solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile(4.92 g) in triethyl orthoformate (100 ml) was heated under reflux fortwo hours, then stirred at 20° C. for 16 hours and evaporated.Trituration with boiling hexane gave1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(ethoxymethylene)amino]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile(4.05 g), m.p.93-95° C. By proceeding in a similar manner the followingcompound was prepared:

1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-5-[1-(methoxyethylene)amino]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile.This was used directly in the next stage.

Reference Example 14

To a suspension of 35% potassium hydride in oil (0.7 g) in dryN,N-dimethylformamide (DMF) was added a solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(methylsulfinyl)-1H-pyrazole-3-carbonitrile(10.0 g) in dry DMF dropwise at 4° C. over 10 minutes. After stirringfor 20 minutes, vinyl ethyl sulfone (3.13 g) in dry DMF was added during5 hours at 4° C. The mixture was stirred overnight under nitrogen withwarming to 20° C. Ammonium chloride was added at 4° C., and the mixtureextracted (ethyl acetate), washed twice with water, dried (sodiumsulfate) and evaporated. Crystallization from ethylacetate/methanol/hexane gave1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyl)ethylamino]-4-(methylsulfinyl)-1H-pyrazole-3-carbonitrile(4.08 g), m.p.131-132° C. By proceeding in a similar manner thefollowing compounds were prepared:

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(cyanoethyl)amino]-4-(methylsulfinyl)-1H-pyrazole-3-carbonitrile,m.p.55-57° C.;1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-(phenylsulfonyl)ethylamino]-1H-pyrazole-3-carbonitrile,m.p.138-139° C.; and

1-[2-chloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyl)ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.139-140° C.

Reference Example 15

To a solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile(0.5 g) in acetonitrile was added 2-bromoacetamide (0.18 g) in water andcalcium carbonate (0.13 g). The mixture was heated under reflux for 1.5hours, cooled to 25° C. and a solution of sodium hydroxide (0.05 g) inwater added. This was then heated under reflux for one hour, evaporatedand the residue purified by preparative thin-layer chromatographyeluting first with 20% methanol in dichloromethane to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[(aminocarbonylmethyl)amino]-1H-pyrazole-3-carbonitrile(0.089 g), m.p.155-157° C.

Reference Example 16

To a suspension of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile(2 g) in toluene was added methyl magnesium bromide (7 ml of a 1.4Msolution in toluene/THF). The mixture was stirred at 20° C. (1 hr.) andneutralised with saturated ammonium chloride solution. The organic layerwas dried (sodium sulfate), evaporated and the residue purified bychromatography using 40% ethyl acetate in hexane to give3-acetyl-5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole(0.68 g), m.p. 166° C.

Reference Example 17

To a suspension of 35% potassium hydride in oil (1.4 g) in dryN,N-dimethylformamide (DMF) was added a solution of1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-amino-4-(ethylsulfinyl)-1H-pyrazole-3-carbonitrile(5.0 g) in dry DMF at 4° C. and stirred for 40 min. 2-Chloroethyl methylsulfide (1.39 g) was added at 4° C. and the stirred mixture allowed towarm to 20° C. over 40 minutes, then heated to 50° C. for 4 hours and at20° C. for 3 days. Ammonium chloride solution and ethyl acetate wereadded and the organic layer dried (sodium sulfate), evaporated andpurified by column chromatography using 80% methyl t-butyl ether inhexane to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[[-2-(methylthio)ethyl]amino]-4-(ethylsulfinyl)-1H-pyrazole-3-carbonitrile(0.26 g), m.p.126-127° C.

By proceeding in a similar manner there were prepared:

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[-2-(methylthio)ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.111-113° C.1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[-2-(ethylthio)ethylamino]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile,m.p.27.5-29° C.1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-(2-propynyl)amino-1H-pyrazole-3-carbonitrile,m.p.140-141° C.

Reference Example 18

Sulfuryl chloride (1.48 g) was added to methyl disulfide (3.16 g) inmethyl t-butyl ether and stirred for 5 hours to give methyl sulfenylchloride. This was added dropwise over 5 minutes to a solution of5-amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile(4.0 g) heated under reflux in methyl t-butyl ether under nitrogen.After 1 hour the cooled mixture was washed in turn with water, sodiumbicarbonate solution and water, dried (sodium sulfate) and evaporated.Purification by chromatography on silica gel eluting with hexane/ethylacetate (9:1) gave5-amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile(3.15 g), m.p.178-180° C. By proceeding in a similar manner thefollowing compound was prepared:

5-amino-1-[3-chloro-5-(trifluoromethyl)pyrid-2-yl]-4-ethylthio-1H-pyrazole-3-carbonitrile.

Reference Example 19

Step 1

Bromine (0.5 ml) was added over 10 minutes to a stirred solution ofsodium thiocyanate (1.7 g) in anhydrous methanol at −65° C. A solutionof5-amino-1-(2-chloro-4-(trifluoromethyl)phenyl]-1-H-pyrazole-3-carbonitrile(1.5 g) in anhydrous methanol was added over 10-minutes and the stirredmixture allowed to warm to 20° C. over 16-hours. After pouring intowater the precipitate was collected and dried to give5-amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-thiocyanato-1H-pyrazole-3-carbonitrile(1.64 g). HPLC (C-18 column, eluting with 3:1 CH₃CN/H₂O at 1.0 ml/min.)showed the compound as a peak of 86.6% area at 5.11 minutes.

Step 2

Iodomethane (0.7 ml) was injected into a stirred suspension of5-amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-thiocyanato-1H-pyrazole-3-carbonitrile(1.64 g), in methanol at 4° C. A 10% aqueous solution of sodiumhydroxide (2.8 ml) was added and the reaction mixture stirred for 1 hourat 4° C., poured into water and extracted with dichloromethane and ethylacetate. The dried (Na₂SO₄) combined organic phase was evaporated andpurified by flash-chromatography on silica gel eluting with 4:1hexane/ethyl acetate to give, after trituration withhexane/dichloromethane,5-amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile(0.4 g), m.p.129-132° C.

By proceeding in a similar manner as step 1 above there was obtained:

A)5-amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-thiocyanato-1H-pyrazole,which was used in Step 2 with iodomethane to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile,m.p. 147-148° C.

B)5-amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-thiocyanato-1H-pyrazole-3-carbonitrile,which was used directly in step 2 with iodoethane and methanol assolvent to give the5-amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile,m.p.211-214° C.

Reference Example 20

A suspension of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile(9.8 g) and N-iodosuccinimide (8.87 g) was heated at reflux in carbontetrachloride for 3.5 hours, cooled and washed with sodium bisulfitesolution, NaOH solution and water. The dried (magnesium sulfate)solution was evaporated and purified by chromatography on silica geleluting with dichloromethane to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-iodo-1H-pyrazole-3-carbonitrile(4.0 g), m.p.212-214° C.

Reference Example 21

5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-iodo-1H-pyrazole-3-carbonitrile(1.96 g) was stirred with dimethylformamide dimethyl acetal (10 ml) at20° C. for 2 hours, then excess ice/water added and the solid filteredand oven-dried to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-iodo-5-N-(dimethylaminomethyleneamino)-1H-pyrazole-3-carbonitrile(1.53 g), m.p.177-180° C.

Reference Example 22

Activated cadmium was prepared by washing cadmium with hydrochloric acid(10%), water, ethanol and ether and drying. Dibromodifluoromethane(317.2 g) in dry N,N-dimethylformamide (DMF) was added during 1 hour toa mixture of activated cadmium (212.5 g) in dry DMF initially at 0-5° C.and when initiated at below 35° C. with stirring under nitrogen.Hexamethylphosphoramide (1l, dry) was added followed by copper (I)bromide (108.5 g) and, after 15 minutes,1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-iodo-5-N-(dimethylaminomethyleneamino)-1H-pyrazole-3-carbonitrile(100.0 g) and the mixture heated at 75° C. for 2 hours. The cooledmixture was filtered (celite), concentrated, diluted (water) andfiltered. The product was washed (hot water) to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-N-(dimethylaminomethyleneamino)-4-trifluoromethyl-1H-pyrazole-3-carbonitrile(80.9 g), m.p.156-157.5° C.

Reference Example 23

A solution of1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-N-(dimethylaminomethyleneamino)-4-trifluoromethyl-1H-pyrazole-3-carbonitrile(120.5 g) in tetrahydrofuran and hydrochloric acid (6N) was heated atreflux for 24 hours, concentrated and filtered. The solid was mixed withdichloromethane and filtered to give5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H-pyrazole-3-carbonitrile(88.2 g), m.p.191-193° C.

Reference Example 24

A solution of5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile(1.0 g) in tetrahydrofuran was added to anhydrous sodium hydride (0.13g) stirred under nitrogen in tetrahydrofuran at 4° C. After 2 hoursiodomethane (0.34 ml) was added and the mixture stirred at 20° C.overnight and treated with ammonium chloride solution. Extraction (ethylacetate), drying (sodium sulfate) and evaporation was followed bychromatography on silica gel eluting with ethyl acetate/dichloromethane(1:9) to give1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-dimethylamino-4-methylthio-1H-pyrazole-3-carbonitrile(0.5 g), m.p.118-119° C.

MITICIDE, INSECTICIDE, APHICIDE, AND NEMATICIDE USE

The following representative test procedures, using compounds of theinvention, were conducted to determine the pesticidal use and activityof compounds of the invention against: mites; certain insects, includingaphids, two species of caterpillar, a fly, and three species of beetlelarvae (one foliar feeding and two root feeding); and nematodes. Thespecific species tested were as follows:

GENUS, SPECIES COMMON NAME (ABBREVIATION) Tetranychus urticae twospottedspider mite TSM Aphis nasturtii buckthorn aphid BA Spodoptera eridaniasouthern armyworm SAW Epilachna varivestis Mexican bean beetle MBB Muscadomestica housefly HF Diabrotica u. howardi southern corn rootworm SCRWDiabrotica virgifera western corn rootworm WCRW Meloidogyne incognitasouthern root-knot SRKN nematode Aphis gossypii cotton aphid CASchizaphis graminum greenbug (aphid) GB Heliothis virescens tobaccobudworm TBW

Formulations:

The test compounds were formulated for use according to the followingmethods used for each of the test procedures.

For mite, aphid, southern armyworm, Mexican bean beetle, and tobaccobudworm tests, a solution or suspension was prepared by adding 10 mg ofthe test compound to a solution of 160 mg of dimethylformamide, 838 mgof acetone, 2 mg of a 3:1 ratio of Triton X-172:Triton X-152(respectively, mainly anionic and nonionic low foam emulsifiers whichare each anhydrous blends of alkylaryl polyether alcohols with organicsulfonates), and 98.99 g of water. The result was a concentration of 100ppm of the test compound.

For housefly tests, the formulation was initially prepared in a similarmanner to the above, but in 16.3 g of water with correspondingadjustment of other components, providing a 200 ppm concentration. Finaldilution with an equal volume of a 20% by weight aqueous solution ofsucrose provided a 100 ppm concentration of the test compound. Whennecessary, sonication was provided to insure complete dispersion.

For southern and western corn rootworm tests, a solution or suspensionwas prepared in the same manner as that used for the initial 200 ppmconcentration for housefly. Aliquots of this 200 ppm formulation werethen used by dilution with water according to the required testconcentration.

For southern root-knot nematode and systemic tests for southernarmyworm, cotton aphid, tobacco budworm and greenbug, a stock solutionor suspension was prepared by adding 15 mg of the test compound to 250mg of dimethylformamide, 1250 mg of acetone and 3 mg of the emulsifierblend referenced above. Water was then added to provide a test compoundconcentration of 150 ppm. When necessary, sonication was provided toinsure complete dispersion.

For tobacco budworm contact tests, a stock solution was prepared bydissolving the compound in acetone and then further diluted to providethe required serial dilution concentrations.

Test Procedures:

The above formulated test compounds were then evaluated for theirpesticidal activity at the specified concentrations, in ppm (parts permillion) by weight, according to the following test procedures:

Twospotted spider mite: Leaves infested with adult and nymphal stages ofthe two-spotted spider mite, obtained from a stock culture were placedon the primary leaves of two bean plants growing in a 6 cm. peat pot. Asufficient number of mites (150-200) for testing were transferred to thefresh plants within a period of twenty-four hours. The potted plants(one pot per compound) were placed on a revolving turntable and sprayed,sufficient to wet the plants to runoff, with 100 ml of the 100 ppm testcompound formulation by use of a DeVilbiss spray gun set at 40 psig. airpressure. As an untreated control, 100 ml of thewater-acetone-DMF-emulsifier solution, containing no test compound, werealso sprayed on infested plants. A treated control with a commercialtechnical compound, either dicofol or hexythiazox, formulated in thesame manner, was tested as a standard. The sprayed plants were held forsix days, after which a mortality count of motile forms was made.

Twospotted spider mite (ovicide test): Eggs were obtained from adults ofthe twospotted spider mite from a stock culture. Heavily infested leavesfrom the stock culture were placed on uninfested bean plants. Femaleswere allowed to oviposit for a period of about 24 hours, after which theleaves of the plant were dipped into a solution of TEPP (tetraethyldiphosphate) in order to kill the motile forms and prevent additionalegg laying. This dipping procedure, which was repeated after the plantsdried, did not affect the viability of the eggs. The potted plants (onepot per compound) were placed on a revolving turntable and sprayed,sufficient to wet the plants to runoff, with 100 ml of the 100 ppm testcompound formulation by use of a DeVilbiss spray gun set at 40 psig. airpressure. As an untreated control, 100 ml of thewater-acetone-DMF-emulsifier solution, containing no test compound, werealso sprayed on infested plants. A treated control with a commercialtechnical compound, typically demeton, formulated in the same manner,was tested as a standard. The sprayed plants were held for seven days,after which a mortality count of egg forms was made along with notationson residual activity on hatched larvae.

Buckthorn or cotton aphid: Adult and nymphal stages of buckthorn orcotton aphid were reared on potted dwarf nasturtium or cotton plants,respectively. The potted plants (one pot per compound tested) infestedwith 100-150 aphids, were placed on a revolving turntable and sprayedwith 100 ml of the 100 ppm test compound formulation by use of aDeVilbiss spray gun set at 40 psig air pressure. As an untreatedcontrol, 100 ml of a water-acetone-DMF-emulsifier solution, containingno test compound, were also sprayed on infested plants. A treatedcontrol with a commercial technical compound, malathion or cyhalothrin,formulated in the same manner, was tested as a standard. After spraying,the pots were stored for one day on buckthorn aphid or three days forcotton aphid, after which the dead aphids were counted.

Southern armyworm: Potted bean plants, were placed on a revolvingturntable and sprayed with 100 ml of the 100 ppm test compoundformulation by use of a DeVilbiss spray gun set at 40 psig air pressure.As an untreated control, 100 ml of a water-acetone-DMF-emulsifiersolution, containing no test compound, were also sprayed on plants. Atreated control with a commercial technical compound, eithercypermethrin or sulprofos, formulated in the same manner, was tested asa standard. When dry, the leaves were placed in plastic cups lined withmoistened filter paper. Five randomly selected second instar southernarmyworm larvae were introduced into each cup which was closed and heldfor five days. Larvae which were unable to move the length of the body,even upon stimulation by prodding, were considered dead.

Tobacco budworm: Potted cotton plants were placed on a revolvingturntable and sprayed with 100 ml of the 100 ppm test compoundformulation by use of a DeVilbiss spray gun set at 40 psig air pressure.As an untreated control, 100 ml of a water-acetone-DMF-emulsifiersolution, containing no test compound, were also sprayed on plants. Atreated control with a commercial technical compound, eithercypermethrin or sulprofos, formulated in the same manner, was tested asa standard. When dry, the leaves were placed in plastic dishescontaining a piece of filter paper and a moistened dental wick. Onerandomly selected second instar tobacco budworm larva was thenintroduced into each cup which was closed and held for five days. Larvaeunable to move the length of their body, even upon stimulation byprodding, were considered dead.

Mexican bean beetle: Potted bean plants were placed on a revolvingturntable and sprayed with 100 ml of the 100 ppm test compoundformulation, sufficient to wet the plants to runoff, by use of aDeVilbiss spray gun set at 40 psig air pressure. As an untreatedcontrol, 100 ml of a water-acetone-DMF-emulsifier solution, containingno test compound, were also sprayed on plants. A treated control with acommercial technical compound, either cypermethrin or sulprofos,formulated in the same manner, was tested as a standard. When dry, theleaves were placed in plastic cups lined with moistened filter paper.Five randomly selected second instar Mexican bean beetle larvae wereintroduced into each cup which was closed and held for five days. Larvaewhich were unable to move the length of the body, even upon stimulationby prodding, were considered dead.

House fly: Four to six day old adult house flies were reared accordingto the specifications of the Chemical Specialties ManufacturingAssociation (Blue Book, McNair-Dorland Co., N.Y. 1954; pages 243-244,261) under controlled conditions. The flies were immobilized byanesthetizing with carbon dioxide and twenty five immobilizedindividuals, males and females, were transferred to a cage consisting ofa standard food strainer and a wrapping-paper-covered surface. Ten ml ofthe 100 ppm test compound formulation were added to a souffle cupcontaining an absorbent cotton pad. As an untreated control, 10 ml of awater-acetone-DMF-emulsifier-sucrose solution, containing no testcompound, were applied in a similar manner. A treated control with acommercial technical compound, malathion, formulated in the same manner,was tested as a standard. The bait cup was introduced inside the foodstrainer prior to admitting the anesthetized flies. After 24 hours,flies which showed no sign of movement on stimulation were considereddead.

Southern or western corn rootworm: Into a jar containing 60 g of sandyloam soil was added 1.5 ml of an aqueous formulation consisting of analiquot of the 200 ppm test compound formulation, diluted with water asappropriate for the final soil concentration of the test compound, 3.2ml of water and five pregerminated corn seedlings. The jar was shakenthoroughly to obtain an even distribution of the test formulation.Following this, twenty corn rootworm eggs (or optionally ten firstinstar larvae in the case of WCRW) were placed into a cavity, which wasmade in the soil.

Vermiculite (1 ml), used optionally in the case of WCRW tests, and water(1.7 ml) were then added to this cavity. In a similar manner, anuntreated control was prepared by application of the same size aliquotof a water-acetone-DMF-emulsifier solution, containing no test compound.Additionally, a treated control with a commercial technical compound(selected typically from terbufos, fonofos, phorate, chlorpyrifos,carbofuran, isazophos, or ethoprop), formulated in the same manner wasused as needed as a test standard. After 7 days, the living rootwormlarvae were counted using a well known “Berlese” funnel extractionmethod.

Southern root-knot nematode: Infected roots of tomato plants, containingegg masses of southern root-knot nematode, were removed from a stockculture and cleaned of soil by shaking and washing with tap water. Thenematode eggs were separated from the root tissue and rinsed with water.Samples of the egg suspension were placed on a fine screen over areceiving bowl, in which the water level was adjusted to be in contactwith the screen. From the bowl, juveniles were collected on a finescreen. The bottom of a cone-shaped container was plugged with coarsevermiculite and then filled to within 1.5 cm of the top with about a 200ml volume of pasteurized soil. Then into a hole made in the center ofthe soil in the cone was pipetted an aliquot of the 150 ppm testcompound formulation. A treated control with a commerical technicalcompound, fenamifos, formulated in a similar manner, was tested as astandard. As an untreated control, an aliquot of awater-acetone-DMF-emulsifier solution, containing no test compound, wasapplied in a similar manner. Immediately after treatment of the soilwith the test compound there were added to the top of each cone 1000second stage juvenile southern root-knot nematodes. After 3 days, asingle healthy tomato seedling was then transplanted into the cone. Thecone, containing the infested soil and tomato seedling, was kept in thegreenhouse for 3 weeks. At the termination of the test, roots of thetomato seedling were removed from the cone and evaluated for galling ona rating scale relative to the untreated control as follows:

1—severe galling, equal to untreated control

3—light galling

4—very light galling

5—no galling, ie, complete control

These results were then converted to an ED₃ or ED₅ value (effective doseto provide a 3 or 5 gall rating).

Southern armyworm on tomato—systemic evaluation: This test was conductedin conjunction with the southern root-knot nematode evaluation(discussed below). The tomato plants, grown in the soil (at an initialcompound test screening rate of 6.6 ppm soil concentration or about 150ppm solution concentration) for nematode evaluation, were then utilizedfor evaluation of a compound's uptake via roots and subsequent systemictransport to the tomato foliage. At the termination of the nematodetest, 21 days after treatment, the tomato foliage was excised, placedinto a plastic container, and infested with second instar larvae ofsouthern armyworm. After about 5 days, the larvae were examined forpercent mortality.

Cotton aphid and tobacco budworm (on cotton) and greenbug and tobaccobudworm (on sorghum)—systemic evaluation: A 7.0 ml aliquot of the 150ppm nematode test solution was applied to deliver the equivalent of 10.0ppm soil concentration dose as a drench to 6 cm pots containing cottonand sorghum plants. The cotton plants were previously infested withcotton aphids about two days before treatment and greenbug one daybefore treatment. After holdiing the plants about three days, the plantswere rated for aphid activity. Again at six days, the plants were ratedfor aphid activity and the cotton aphids and greenbugs were counted andmortality was assessed. Portions of the cotton and sorghum foliage wereexcised, placed in separate plastic containers, and infested with secondinstar larvae of tobacco budworm. The potted plants were dipped insulfotepp to kill the remaining aphids and returned to the greenhousefor regrowth. Thirteen days after treatment, the remaining foliage wasexcised and fed to tobacco budworms. Mortality was assessed six daysafter infestation.

Cotton aphid and southern armyworm (on cotton) and greenbug and southernarmyworm (on sorghum)—systemic evaluation: A stock solution orsuspension was prepared to deliver 5 ml of a 20 ppm soil concentrationdose (and subsequent dilutions) as a drench to 6 cm pots containingcotton and sorghum plants. The cotton plants were previously infestedwith cotton aphids about two days before treatment and greenbug one daybefore treatment. After holding the plants about three days, the plantswere rated for aphid activity. Again at six days, the plants were ratedfor aphid activity and the cotton aphids and greenbugs were counted andmortality was assessed. Portions of the cotton and sorghum foliage wereexcised, placed in separate plastic containers, and infested with secondinstar larvae of southern armyworms. The potted plants were dipped insulfotepp to kill the remaining aphids and returned to the greenhousefor regrowth. Thirteen days after treatment the remaining foliage wasexcised and fed to southern armyworm. Mortality was assessed six daysafter infestation.

Cotton aphid and southern armyworm (on cotton and oats)—seed treatmentevaluation: Technical material was applied to the seed of oats andcotton by placing the compound and the seed in an appropriate sized jarand rolling the jar on a ball mill. Assay of the material applied to theseed was by weight. Seed was then planted. When germinated and emerged,the plants were infested at the appropriate intervals with host insects.Mortality was assessed on those insects.

Tobacco budworm—contact evaluation: The following topical applicationmethod provides an assessment of contact toxicity of a compound totobacco budworm larvae. The test compound solution at sequentialtwo-fold dilution concentrations from 10 down to 0.16 μg/μl was appliedby a microinjector in replicated 1 μl portions to the dorsum ofapproximately 20 mg tobacco budworm larvae. This is equivalent toapplied doses of 500 down to 8 μg/g body weight. An acetone treatedcontrol, without any test compounds, was also applied. A treated controlwith a commercial technical compound, cypermethrin or thiodicarb, alsoin acetone was used as a standard. The treated larvae were placed,individually, in separate plastic petri dishes containing an untreatedcotton leaf and a moist dental wick. The treated larvae were maintainedat about 27° C. and 50% relative humidity. The percent mortality wasrated 1 and 4 days after treatment.

All of the Compound Numbers 1 to 118 of the invention showedinsecticidal activity in one or more of the above evaluation methods,with particularly good activity in the systemic tests. Compounds

METHODS AND COMPOSITIONS

The present invention provides a method for the systemic control ofarthropods at a locus, especially some insects or mites which feed onthe above ground portions of plants. Control of such foliar pests may beprovided by direct foliar application or by application by for examplesoil spray or granule application to the plant roots or plant seeds withsubsequent systemic translocation to the above ground portions of theplants. Such systemic activity includes the control of insects whichreside not only at the point of application but at a remote part of theplant for example by translocation from one side of a leaf to the otheror from a treated leaf to an untreated leaf. Examples of the classes ofinsect pests which may be systemically controlled by the arylpyrazolesof the invention include the Homoptera order (piercing-sucking),Hemiptera order (piercing-sucking), and Thysanoptera order. Theinvention is especially appropriate for aphids and thrips.

As is evident from the foregoing pesticidal uses, the present inventionprovides pesticidally active arylpyrazoles and methods of use of saidarylpyrazoles for the control of a number of pest species whichincludes: arthropods, especially insects or mites; plant nematodes; orhelminth or protozoan pests. The arylpyrazoles of formula (I) orpesticidally acceptable salts thereof thus are advantageously employedin practical uses, for example, in agricultural or horticultural crops,forestry, veterinary medicine or livestock husbandry, or in publichealth. From this point forward, whenever the term “arylpyrazoles offormula (I)” is used this term embraces arylpyrazoles of formula (I) andtheir pesticidally acceptable salts. The term “arylpyrazole of formula(I)” embraces a arylpyrazole of formula (I) and a pesticidallyacceptable salt thereof.

The present invention therefore provides a method of control of pests ata locus which comprises the treatment of the locus (e.g., by applicationor administration) with an effective amount of a arylpyrazole of formula(I) or a pesticidally acceptable salt thereof, wherein the substituentgroups are as hereinbefore defined. The locus includes, for example, thepest itself or the place (plant, animal, field, structure, premises,forest, orchard, waterway, soil, plant or animal product, or the like)where the pest resides or feeds.

The arylpyrazoles of this invention may in addition be used to controlsoil insects, such as corn rootworm, termites (especially for protectionof structures), root maggots, wireworms, root weevils, stalkborers,cutworms, root aphids, or grubs. They may also be used to provideactivity against plant pathogenic nematodes, such as root-knot, cyst,dagger, lesion, or stem or bulb nematodes, or against mites. For thecontrol of soil pests, for example corn rootworm, the arylpyrazoles areadvantageously applied to or incorporated at an effective rate into thesoil in which crops are planted or to be planted or to the seeds orgrowing plant roots.

In the area of public health, the arylpyrazoles are especially useful inthe control of many insects, especially filth flies or other Dipteranpests, such as houseflies, stableflies, soldierflies, hornflies,deerflies, horseflies, midges, punkies, blackflies, or mosquitoes.

Arylpyrazoles of the invention may be used in the following applicationsand on the following pests including arthropods, especially insects ormites, nematodes, or helminth or protozoan pests:

In the protection of stored products, for example cereals, includinggrain or flour, groundnuts, animal feedstuffs, timber or householdgoods, e.g. carpets and textiles, arylpyrazoles of the invention areuseful against attack by arthropods, more especially beetles, includingweevils, moths or mites, for example Ephestia spp. (flour moths),Anthrenus spp. (carpet beetles), Tribolium spp. (flour beetles),Sitophilus spp. (grain weevils) or Acarus spp. (mites).

In the control of cockroaches, ants or termites or similar arthropodpests in infested domestic or industrial premises or in the control ofmosquito larvae in waterways, wells, reservoirs or other running orstanding water.

For the treatment of foundations, structures or soil in the preventionof the attack on building by termites, for example, Reticulitermes spp.,Heterotermes spp., Coptotermes spp.

In agriculture against adults, larvae and eggs of Lepidoptera(butterflies and moths), e.g. Heliothis spp. such as Heliothis virescens(tobacco budworm), Heliothis armigera and Heliothis zea. Against adultsand larvae of Coleoptera (beetles) e.g. Anthonomus spp. e.g. grandis(cotton boll weevil), Leptinotarsa decemlineata (Colorado potatobeetle), Diabrotica spp. (corn rootworms). Against Heteroptera(Hemiptera and Homoptera) e.g. Psylla spp., Bemisia spp., Trialeurodesspp., Aphis spp., Myzus spp., Megoura viciae, Phylloxera spp.,Nephotettix spp. (rice leaf hoppers), Nilaparvata spp.

Against Diptera e.g. Musca spp. Against Thysanoptera such as Thripstabaci. Against Orthoptera such as Locusta and Schistocerca spp.,(locusts and crickets) e.g. Gryllus spp., and Acheta spp. for example,Blatta orientalis, Periplaneta americana, Blatella germanica, Locustamigratoria migratorioides, and Schistocerca gregaria. Against Collembolae.g. Periplaneta spp. and Blattela spp. (roaches). Against Isoptera e.g.Coptotermes spp. (termites).

Against arthropods of agricultural significance such as Acari (mites)e.g. Tetranychus spp., and Panonychus spp.

Against nematodes which attack plants or trees of importance toagriculture, forestry or horticulture either directly or by spreadingbacterial, viral, mycoplasma or fungal diseases of the plants. Forexample root-knot nematodes such as Meloidogyne spp. (e.g. M.incognita).

In the field of veterinary medicine or livestock husbandry or in themaintenance of public health against arthropods, helminths or protozoawhich are parasitic internally or externally upon vertebrates,particularly warm-blooded vertebrates, for example domestic animals,e.g. cattle, sheep, goats, equines, swine, poultry, dogs or cats, forexample Acarina, including ticks (e.g. Ixodes spp., Boophilus spp. e.g.Boophilus microplus, Rhipicephalus spp. e.g. Rhipicephalusappendiculatus Ornithodorus spp. (e.g. Ornithodorus moubata) and mites(e.g. Damalinia spp.); Diptera (e.g. Aedes spp., Anopheles spp., Muscaspp., Hypoderma spp.); Hemiptera.; Dictyoptera (e.g. Periplaneta spp.,Blatella spp.); Hymenoptera; for example against infections of thegastro-intestinal tract caused by parasitic nematode worms, for examplemembers of the family Trichostrongylidae; in the control and treatmentof protozoal diseases caused by, for example, Eimeria spp. e.g.Trypanosoms cruzi, Leishaminia spp., Plasmodium spp., Babesis spp.,Trichomonadidae spp., Toxoplasma spp. and Theileria spp.

In practical use for the control of arthropods, especially insects ormites, or nematode pests of plants, a method, for example, comprisesapplying to the plants or to the medium in which they grow an effectiveamount of a arylpyrazole of the invention. For such a method; the activearylpyrazole is generally applied to the locus in which the arthropod ornematode infestation is to be controlled at an effective rate in therange of about 5 g to about 1 kg of the active arylpyrazole per hectareof locus treated. Under ideal conditions, depending on the pest to becontrolled, a lower rate may offer adequate protection. On the otherhand, adverse weather conditions, resistance of the pest or otherfactors may require that the active ingredient be used at higher rates.The optimum rate depends usually upon a number of factors, for example,the type of pest being controlled, the type or the growth stage of theinfested plant, the row spacing or also the method of application. Morepreferably an effective rate range of the active arylpyrazole is fromabout 50 g/ha to about 400 g/ha.

When a pest is soil-borne, the active arylpyrazole generally in aformulated composition, is distributed evenly over the area to betreated (ie, for example broadcast or band treatment) in any convenientmanner and is applied at rates from about 5 to about 1 kg ai/ha,preferably from about 50 to about 250 g ai/ha. When applied as a rootdip to seedlings or drip irrigation to plants the liquid solution orsuspension contains from about 0.075 to about 1000 mg ai/l, preferablyfrom about 25 to about 200 mg ai/l. Application may be made, if desired,to the field or crop-growing area generally or in close proximity to theseed or plant to be protected from attack. The active component can bewashed into the soil by spraying with water over the area or can be leftto the natural action of rainfall. During or after application, theformulated arylpyrazole can, if desired, be distributed mechanically inthe soil, for example by ploughing, disking, or use of drag chains.Application can be prior to planting, at planting, after planting butbefore sprouting has taken place, or after sprouting.

The arylpyrazoles of the invention and methods of control of peststherewith are of particular value in the protection of field, forage,plantation, glasshouse, orchard or vineyard crops, of ornamentals, or ofplantation or forest trees, for example: cereals (such as wheat orrice), cotton, vegetables (such as peppers), field crops (such as sugarbeets, soybeans or oil seed rape), grassland or forage crops (such asmaize or sorghum), orchards or groves (such as of stone or pit fruit orcitrus), ornamental plants, flowers or vegetables or shrubs under glassor in gardens or parks, or forest trees (both deciduous and evergreen)in forests, plantations or nurseries.

They are also valuable in the protection of timber (standing, felled,converted, stored or structural) from attack, for example, by sawfliesor beetles or termites.

They have applications in the protection of stored products such asgrains, fruits, nuts, spices or tobacco, whether whole, milled orarylpyrazoleed into products, from moth, beetle, mite or grain weevilattack. Also protected are stored animal products such as skins, hair,wool or feathers in natural or converted form (e.g. as carpets ortextiles) from moth or beetle attack as well as stored meat, fish orgrains from beetle, mite or fly attack.

Additionally, the arylpyrazoles of the invention and methods of usethereof are of particular value in the control of arthropods, helminthsor protozoa which are injurious to, or spread or act as vectors ofdiseases domestic animals, for example those hereinbefore mentioned, andmore especially in the control of ticks, mites, lice, fleas, midges, orbiting, nuisance or myiasis flies. The arylpyrazoles of the inventionare particularly useful in controlling arthropods, helminths or protozoawhich are present inside domestic host animals or which feed in or onthe skin or suck the blood of the animal, for which purpose they may beadministered orally, parenterally, percutaneously or topically.

Furthermore, arylpyrazoles of the invention may be useful forcoccidiosis, a disease caused by infections from protozoan parasites ofthe genus Eimeria. It is an important potential cause of economic lossin domestic animals and birds, particularly those raised or kept underintensive conditions. For example, cattle, sheep, pigs or rabbits may beaffected, but the disease is especially important in poultry,particularly in chickens. Administration of a small amount of aarylpyrazole of the invention, preferably by a combination with feed iseffective in preventing or greatly reducing the incidence ofcoccidiosis. The arylpyrazoles are effective against both the cecal formand the intestinal forms. Furthermore, the arylpyrazoles of theinvention may also exert an inhibiting effect on oocytes by greatlyreducing the number and sporulation of those produced. The poultrydisease is generally spread by the birds picking up the infectiousorganism in droppings in or on contaminated litter, ground, food, ordrinking water. The disease is manifested by hemorrhage, accumulation ofblood in the ceca, passage of blood to the droppings, weakness anddigestive disturbances. The disease often terminates in the death of theanimal, but the fowl which survive severe infections have had theirmarket value subtantially reduced as a result of the infection.

The compositions hereinafter described for application to growing cropsor crop growing loci or as a seed dressing may, in general,alternatively be employed for topical application to animals or in theprotection of stored products, household goods, property or areas of thegeneral environment. Suitable means of applying the arylpyrazoles of theinvention include:

to growing crops as foliar sprays, dusts, granules, fogs or foams oralso as suspensions of finely divided or encapsulated compositions assoil or root treatments by liquid drenches, dusts, granules, smokes orfoams; to seeds of crops via application as seed dressings by liquidslurries or dusts;

to animals infested by or exposed to infestation by arthropods,helminths or protozoa, by parenteral, oral or topical application ofcompositions in which the active ingredient exhibits an immediate and/orprolonged action over a period of time against the arthropods, helminthsor protozoa, for example by incorporation in feed or suitableorally-ingestible pharmaceutical formulations, edible baits, salt licks,dietary supplements, pour-on formulations, sprays, baths, dips, showers,jets, dusts, greases, shampoos, creams, wax smears or livestockself-treatment systems;

to the environment in general or to specific locations where pests maylurk, including stored products, timber, household goods, or domestic orindustrial premises, as sprays, fogs, dusts, smokes, wax-smears,lacquers, granules or baits, or in tricklefeeds to waterways, wells,reservoirs or other running or standing water;

to domestic animals in feed to control fly larvae feeding in theirfeces;

In practice, the arylpyrazoles of the invention most frequently formparts of compositions. These compositions can be employed to control:arthopods, especially insects or mites; nematodes; or helminth orprotozoan pests. The compositions may be of any type known in the artsuitable for application to the desired pest in any premises or indooror outdoor area or by internal or external administration tovertebrates. These compositions contain at least one arylpyrazole offormula (I) or a pesticidally acceptable salt thereof, such as describedearlier, as the active ingredient in combination or association with oneor more other compatible components which are for example, solid orliquid carriers or diluents, adjuvants, surface-active-agents, or thelike appropriate for the intended use and which are agronomically ormedicinally acceptable. These compositions, which may be prepared by anymanner known in the art, likewise form a part of this invention.

These compositions may also contain other kinds of ingredients such asprotective colloids, adhesives, thickeners, thixotropic agents,penetrating agents, spray oils (especially for acaridical use),stabilizers, preservative agents (especially mold preservatives),sequestering agents, or the like, as well as other known activeingredients with pesticidal properties (particularly insecticidal,miticidal, nematicidal, or fungicidal) or with properties regulating thegrowth of plants. More generally, the arylpyrazoles employed in theinvention may be combined with all the solid or liquid additivescorresponding to the usual techniques of formulation.

Compositions, suitable for applications in agriculture, horticulture, orthe like include formulations suitable for use as, for example, sprays,dusts, granules, fogs, foams, emulsions, or the like.

The effective use doses of the arylpyrazoles employed in the inventioncan vary within wide limits, particularly depending on the nature of thepest to be eliminated or degree of infestation, for example, of cropswith these pests. In general, the compositions according to theinvention usually contain about 0.05 to about 95% (by weight) of one ormore active ingredients according to the invention, about 1 to about 95%of one or more solid or liquid carriers and, optionally, about 0.1 toabout 50% of one or more other compatible components, such assurface-active agents or the like.

In the present account, the term “carrier” denotes an organic orinorganic ingredient, natural or synthetic, with which the activeingredient is combined to facilitate its application, for example, tothe plant, to seeds or to the soil. This carrier is therefore generallyinert and it must be acceptable (for example, agronomically acceptable,particularly to the treated plant).

The carrier may be a solid, for example, clays, natural or syntheticsilicates, silica, resins, waxes, solid fertilizers (for exampleammonium salts), ground natural minerals, such as kaolins, clays, talc,chalk, quartz, attapulgite, montmorillonite, bentonite or diatomaceousearth, or ground synthetic minerals, such as silica, alumina, orsilicates especially aluminium or magnesium silicates. As solid carriersfor granules the following are suitable: crushed or fractionated naturalrocks such as calcite, marble, pumice, sepiolite and dolomite; syntheticgranules of inorganic or organic meals; granules of organic materialsuch as sawdust, coconut shells, corn cobs, corn husks or tobaccostalks; kieselguhr, tricalcium phosphate, powdered cork, or absorbentcarbon black; water soluble polymers, resins, waxes; or solidfertilizers. Such solid compositions may, if desired, contain one ormore compatible wetting, dispersing, emulsifying or colouring agentswhich, when solid, may also serve as a diluent.

The carrier may also be liquid, for example: water; alcohols,particularly butanol or glycol, as well as their ethers or esters,particularly methylglycol acetate; ketones, particularly acetone,cyclohexanone, methylethyl ketone, methylisobutylketone, or isophorone;petroleum fractions such as paraffinic or aromatic hydrocarbons,particularly xylenes or alkyl naphthalenes; mineral or vegetable oils;aliphatic chlorinated hydrocarbons, particularly trichloroethane ormethylene chloride; aromatic chlorinated hydrocarbons, particularlychlorobenzenes; water-soluble or strongly polar solvents such asdimethylformamide, dimethyl sulphoxide, or N-methylpyrrolidone;liquefied gases; or the like or a mixture thereof.

The surface-active agent may be an emulsifying agent, dispersing agentor wetting agent of the ionic or non-ionic type or a mixture of suchsurface-active agents. Amongst these are e.g., salts of polyacrylicacids, salts of lignosulphonic acids, salts of phenolsulphonic ornaphthalenesulphonic acids, polycondensates of ethylene oxide with fattyalcohols or fatty acids or fatty esters or fatty amines, substitutedphenols (particularly alkylphenols or arylphenols), salts ofsulphosuccinic acid esters, taurine derivatives (particularlyalkyltaurates), phosphoric esters of alcohols or of polycondensates ofethylene oxide with phenols, esters of fatty acids with polyols, orsulphate, sulphonate or phosphate functional derivatives of the abovearylpyrazoles. The presence of at least one surface-active agent isgenerally essential when the active ingredient and/or the inert carrierare only slightly water soluble or are not water soluble and the carrieragent of the composition for application is water.

Compositions of the invention may further contain other additives suchas adhesives or colorants. Adhesives such as carboxymethylcellulose ornatural or synthetic polymers in the form of powders, granules orlattices, such as arabic gum, polyvinyl alcohol or polyvinyl acetate,natural phospholipids, such as cephalins or lecithins, or syntheticphospholipids can be used in the formulations. It is possible to usecolorants such as inorganic pigments, for example: iron oxides, titaniumoxides or Prussian Blue; organic dyestuffs, such as alizarin dyestuffs,azo dyestuffs or metal phthalocyanine dyestuffs; or trace nutrients suchas salts of iron, manganese, boron, copper, cobalt, molybdenum or zinc.

Compositions containing arylpyrazoles of formula (I), or pesticidallyacceptable salts thereof, which may be applied to control arthropod,plant nematode, helminth or protozoan pests, may also contain synergists(e.g. piperonyl butoxide or sesamex), stabilizing substances, otherinsecticides, acaricides, plant nematocides, anthelmintics oranticoccidials, fungicides (agricultural or veterinary as appropriate,e.g. benomyl and iprodione), bactericides, arthropod or vertebrateattractants or repellents or pheromones, deodorants, flavouring agents,dyes, or auxiliary therapeutic agents, e.g. trace elements. These may bedesigned to improve potency, persistence, safety, uptake where desired,spectrum of pests controlled or to enable the composition to performother useful functions in the same animal or area treated.

Examples of other pesticidally-active arylpyrazoles which may beincluded in, or used in conjunction with the compositions of the presentinvention are: acephate, chlorpyrifos, demeton-S-methyl, disulfoton,ethoprofos, fenitrothion, fenamiphos, fonofos, isazophos, isofenphos,malathion, monocrotophos, parathion, phorate, phosalone,pirimiphos-methyl, terbufos, triazophos, cyfluthrin, cypermethrin,deltamethrin, fenpropathrin, fenvalerate, permethrin, tefluthrin,aldicarb, carbosulfan, methomyl, oxamyl, pirimicarb, bendiocarb,teflubenzuron, dicofol, endosulfan, lindane, benzoximate, cartap,cyhexatin, tetradifon, avermectins, ivermectins, milbemycins,thiophanate, trichlorfon, dichlorvos, diaveridine or dimetriadazole.

For their agricultural application, the arylpyrazoles of the formula(I), or pesticidally acceptable salts thereof, are therefore generallyin the form of compositions, which are in various solid or liquid forms.

Solid forms of compositions which can be used are dusting powders (witha content of the arylpyrazole of formula (I), or a pesticidallyacceptable salt thereof, ranging up to 80%), wettable powders orgranules (including water dispersible granules), particularly thoseobtained by extrusion, compacting, impregnation of a granular carrier,or granulation starting from a powder (the content of the arylpyrazoleof formula (I), or a pesticidally acceptable salt thereof, in thesewettable powders or granules being between about 0.5 and about 80%).Solid homogenous or heterogenous compositions containing one or morearylpyrazoles of formula (I), or pesticidally acceptable salts thereof,for example granules, pellets, briquettes or capsules, may be used totreat standing or running water over a period of time. A similar effectmay be achieved using trickle or intermittent feeds of water dispersibleconcentrates as described herein.

Liquid compositions, for example, include aqueous or non-aqueoussolutions or suspensions (such as emulsifiable concentrates, emulsions,flowables, dispersions, or solutions) or aerosols. Liquid compositionsalso include, in particular, emulsifiable concentrates, dispersions,emulsions, flowables, aerosols, wettable powders (or powder forspraying), dry flowables or pastes as forms of compositions which areliquid or intended to form liquid compositions when applied, for exampleas aqueous sprays (including low and ultra-low volume) or as fogs oraerosols.

Liquid compositions, for example, in the form of emulsifiable or solubleconcentrates most frequently comprise about 5 to about 80% by weight ofthe active ingredient, while the emulsions or solutions which are readyfor application contain, in their case, about 0.01 to about 20% of theactive ingredient. Besides the solvent, the emulsifiable or solubleconcentrates may contain, when required, about 2 to about 50% ofsuitable additives, such as stabilizers, surface-active agents,penetrating agents, corrosion inhibitors, colorants or adhesives.Emulsions of any required concentration, which are particularly suitablefor application, for example, to plants, may be obtained from theseconcentrates by dilution with water. These compositions are includedwithin the scope of the compositions which may be employed in thepresent invention. The emulsions may be in the form of water-in-oil oroil-in-water type and they may have a thick consistency.

The liquid compositions of this invention may, in addition to normalagricultural use applications be used for example to treat substrates orsites infested or liable to infestation by arthropods (or other pestscontrolled by arylpyrazoles of this invention) including premises,outdoor or indoor storage or processing areas, containers or equipmentor standing or running water.

All these aqueous dispersions or emulsions or spraying mixtures can beapplied, for example, to crops by any suitable means, chiefly byspraying, at rates which are generally of the order of about 100 toabout 1,200 liters of spraying mixture per hectare, but may be higher orlower (eg. low or ultra-low volume) depending upon the need orapplication technique. The arylpyrazoles or compositions according tothe invention are conveniently applied to vegetation and in particularto roots or leaves having pests to be eliminated. Another method ofapplication of the arylpyrazoles or compositions according to theinvention is by chemigation, that is to say, the addition of aformulation containing the active ingredient to irrigation water. Thisirrigation may be sprinkler irrigation for foliar pesticides or it canbe ground irrigation or underground irrigation for soil or for systemicpesticides.

The concentrated suspensions, which can be applied by spraying, areprepared so as to produce a stable fluid product which does not settle(fine grinding) and usually contain from about 10 to about 75% by weightof active ingredient, from about 0.5 to about 30% of surface-activeagents, from about 0.1 to about 10% of thixotropic agents, from about 0to about 30% of suitable additives, such as anti-foaming agents,corrosion inhibitors, stabilizers, penetrating agents, adhesives and, asthe carrier, water or an organic liquid in which the active ingredientis poorly soluble or insoluble. Some organic solids or inorganic saltsmay be dissolved in the carrier to help prevent settling or asantifreezes for water.

The wettable powers (or powder for spraying) are usually prepared sothat they contain from about 10 to about 80% by weight of activeingredient, from about 20 to about 90% of a solid carrier, from about 0to about 5% of a wetting agent, from about 3 to about 10% of adispersing agent and, when necessary, from about 0 to about 80% of oneor more stabilizers and/or other additives, such as penetrating agents,adhesives, anti-caking agents, colorants, or the like. To obtain thesewettable powders, the active ingredient(s) is(are) thoroughly mixed in asuitable blender with additional substances which may be impregnated onthe porous filler and is(are) ground using a mill or other suitablegrinder. This produces wettable powders, the wettability and thesuspendability of which are advantageous. They may be suspended in waterto give any desired concentration and this suspension can be employedvery advantageously in particular for application to plant foliage.

The “water dispersible granules (WG)” (granules which are readilydispersible in water) have compositions which are substantially close tothat of the wettable powders. They may be prepared by granulation offormulations described for the wettable powders, either by a wet route(contacting finely divided active ingredient with the inert filler and alittle water, e.g. 1 to 20% by weight, or with an aqueous solution of adispersing agent or binder, followed by drying and screening), or by adry route (compacting followed by grinding and screening).

The rates and concentrations of the formulated compositions may varyaccording to the method of application or the nature of the compositionsor use thereof. Generally speaking, the compositions for application tocontrol arthropod, plant nematode, helminth or protozoan pests usuallycontain from about 0.00001% to about 95%, more particularly from about0.0005% to about 50% by weight of one or more arylpyrazoles of formula(I), or pesticidally acceptable salts thereof, or of total activeingredients (that is to say the arylpyrazole of formula (I), or apesticidally acceptable salt thereof, together with: other substancestoxic to arthropods or plant nematodes, anthelmintics, anticoccidials,synergists, trace elements or stabilizers). The actual compositionsemployed and their rate of application will be selected to achieve thedesired effect(s) by the farmer, livestock producer, medical orveterinary practitioner, pest control operator or other person skilledin the art.

Solid or liquid compositions for application topically to animals,timber, stored products or household goods usually contain from about0.00005% to about 90%, more particularly from about 0.001% to about 10%,by weight of one or more arylpyrazoles of formula (I) or pesticidallyacceptable salts thereof. For administration to animals orally orparenterally, including percutaneously solid or liquid compositions,these normally contain from about 0.1% to about 90% by weight of one ormore arylpyrazoles of formula (I) or pesticidally acceptable saltsthereof. Medicated feedstuffs normally contain from about 0.001% toabout 3% by weight of one or more arylpyrazoles of formula (I) orpesticidally acceptable salts thereof. Concentrates or supplements formixing with feedstuffs normally contain from about 5% to about 90%,preferably from about 5% to about 50%, by weight of one or morearylpyrazoles of formula (I) or pesticidally acceptable salts thereof.Mineral salt licks normally contain from about 0.1% to about 10% byweight of one or more arylpyrazoles of formula (I) or pesticidallyacceptable salts thereof.

Dusts or liquid compositions for application to livestock, goods,premises or outdoor areas may contain from about 0.0001% to about 15%,more especially from about 0.005% to about 2.0%, by weight, of one ormore arylpyrazoles of formula (I) or pesticidally acceptable saltsthereof. Suitable concentrations in treated waters are between about0.0001 ppm and about 20 ppm, more particularly about 0.001 ppm to about5.0 ppm. of one or more arylpyrazoles of formula (I), or pesticidallyacceptable salts thereof, and may be used therapeutically in fishfarming with appropriate exposure times. Edible baits may contain fromabout 0.01% to about 5%, preferably from about 0.01% to about 1.0%, byweight, of one or more arylpyrazoles of formula (I) or pesticidallyacceptable salts thereof.

When administered to vertebrates parenterally, orally or by percutaneousor other means, the dosage of arylpyrazoles of formula (I), orpesticidally acceptable salts thereof, will depend upon the species,age, or health of the vertebrate and upon the nature and degree of itsactual or potential infestation by arthropod, helminth or protozoanpests. A single dose of about 0.1 to about 100 mg, preferably about 2.0to about 20.0 mg, per kg body weight of the animal or doses of about0.01 to about 20.0 mg, preferably about 0.1 to about 5.0 mg, per kg bodyweight of the animal per day, for sustained medication, are generallysuitable by oral or parenteral administration. By use of sustainedrelease formulations or devices, the daily doses required over a periodof months may be combined and administered to animals on a singleoccasion.

The following composition EXAMPLES 2A-2M illustrate compositions for useagainst arthropods, especially mites or insects, plant nematodes, orhelminth or protozoan pests which comprise, as active ingredient,arylpyrazoles of formula (I), or pesticidally acceptable salts thereof,such as those described in preparative examples. The compositionsdescribed in EXAMPLES 2A-2M can each be diluted to give a sprayablecompositon at concentrations suitable for use in the field. Genericchemical descriptions of the ingredients (for which all of the followingpercentages are in weight percent), used in the composition EXAMPLES2A-2M exemplified below, are as follows:

Trade Name Chemical Description Ethylan BCP Nonylphenol ethylene oxidecondensate Soprophor BSU Tristyrylphenol ethylene oxide condensateArylan CA A 70% w/v solution of calcium dodecylbenzenesulfonate Solvesso150 Light C₁₀ aromatic solvent Arylan S Sodium dodecylbenzenesulfonateDarvan No2 Sodium lignosulphonate Celite PF Synthetic magnesium silicatecarrier Sopropon T36 Sodium salts of polycarboxylic acids Rhodigel 23Polysaccharide xanthan gum Bentone 38 Organic derivative of magnesiummontmorillonite Aerosil Microfine silicon dioxide

Example 2A

A water soluble concentrate is prepared with the composition as follows:

Active ingredient  7% Ethylan BCP 10% N-methylpyrrolidone 83%

To a solution of Ethylan BCP dissolved in a portion ofN-methylpyrrolidone is added the active ingredient with heating andstirring until dissolved. The resulting solution is made up to volumewith the remainder of the solvent.

Example 2B

An emulsifiable concentrate (EC) is prepared with the composition asfollows:

Active ingredient 25% (max) Soprophor BSU 10% Arylan CA  5%N-methylpyrrolidone 50% Solvesso 150 10%

The first three components are dissolved in N-methylpyrrolidone and tothis is then added the Solvesso 150 to give the final volume.

Example 2C

A wettable powder (WP) is prepared with the composition as follows:

Active ingredient 40% Arylan S 2% Darvan No2 5% Celite PF 53%

The ingredients are mixed and ground in a hammer-mill to a powder with aparticle size of less than 50 microns.

Example 2D

An aqueous-flowable formulation is prepared with the composition asfollows:

Active ingredient 40.00% Ethylan BCP 1.00% Sopropon T360. 0.20% Ethyleneglycol 5.00% Rhodigel 230. 0.15% Water 53.65%

The ingredients are intimately mixed and are ground in a bead mill untila mean particle size of less than 3 microns is obtained.

Example 2E

An emulsifiable suspension concentrate is prepared with the compositionas follows:

Active ingredient 30.0% Ethylan BCP 10.0% Bentone 38  0.5% Solvesso 15059.5%

The ingredients are intimately mixed and ground in a beadmill until amean particle size of less than 3 microns is obtained.

Example 2F

A water dispersible granule is prepared with the composition as follows:

Active ingredient 30% Darvan No 2 15% Arylan S  8% Celite PF 47%

The ingredients are mixed, micronized in a fluid-energy mill and thengranulated in a rotating pelletizer by spraying with water (up to 10%).The resulting granules are dried in a fluid-bed drier to remove excesswater.

Example 2G

A dusting powder is prepared with the composition as follows:

Active ingredient  1 to 10% Talc powder-superfine 99 to 90%

The ingredients are intimately mixed and further ground as necessary toachieve a fine powder. This powder may be applied to a locus ofarthropod infestation, for example refuse dumps, stored products orhousehold goods or animals infested by, or at risk of infestation by,arthropods to control the arthropods by oral ingestion. Suitable meansfor distributing the dusting powder to the locus of arthropodinfestation include mechanical blowers, handshakers or livestock selftreatment devices.

Example 2H

An edible bait is prepared with the composition as follows:

Active ingredient 0.1 to 1.0% Wheat flour 80% Molasses 19.9 to 19%  

The ingredients are intimately mixed and formed as required into a baitform. This edible bait may be distributed at a locus, for exampledomestic or industrial premises, e.g. kitchens, hospitals or stores, oroutdoor areas, infested by arthropods, for example ants, locusts,cockroaches or flies, to control the arthropods by oral ingestion.

Example 2I

A solution formulation is prepared with a composition as follows:

Active ingredient 15% Dimethyl sulfoxide 85%

The active ingredient is dissolved in dimethyl sulfoxide with mixing andor heating as required. This solution may be applied percutaneously as apour-on application to domestic animals infested by arthropods or, aftersterilization by filtration through a polytetrafluoroethylene membrane(0.22 micrometer pore size), by parenteral injection, at a rate ofapplication of from 1.2 to 12 ml of solution per 100 kg of animal bodyweight.

Example 2J

A wettable powder is prepared with the composition as follows:

Active ingredient 50% Ethylan BCP  5% Aerosil  5% Celite PF 40%

The Ethylan BCP is absorbed onto the Aerosil which is then mixed withthe other ingredients and ground in a hammer-mill to give a wettablepowder, which may be diluted with water to a concentration of from0.001% to 2% by weight of the active arylpyrazole and applied to a locusof infestation by arthropods, for example, dipterous larvae or plantnematodes, by spraying, or to domestic animals infested by, or at riskof infection by arthropods, helminths or protozoa, by spraying ordipping, or by oral administration in drinking water, to control thearthropods, helminths or protozoa.

Example 2K

A slow release bolus composition is formed from granules containing thefollowing components in varying percentages(similar to those describedfor the previous compositions) depending upon need:

Active ingredient

Density agent

Slow-release agent

Binder

The intimately mixed ingredients are formed into granules which arecompressed into a bolus with a specific gravity of 2 or more. This canbe administered orally to ruminant domestic animals for retention withinthe reticulo-rumen to give a continual slow release of activearylpyrazole over an extended period of time to control infestation ofthe ruminant domestic animals by arthropods, helminths or protozoa.

Example 2L

A slow release composition in the form of granules, pellets, brickettesor the like can be prepared with compositions as follows:

Active ingredient 0.5 to 25%  Polyvinyl chloride   75 to 99.5% Dioctylphthalate (plasticizer)

The components are blended and then formed into suitable shapes bymelt-extrusion or molding. These composition are useful, for example,for addition to standing water or for fabrication into collars oreartags for attachment to domestic animals to control pests by slowrelease.

Example 2M

A water dispersible granule is prepared with the composition as follows:

Active ingredient 85% (max) Polyvinylpyrrolidone  5% Attapulgite clay 6% Sodium lauryl sulfate  2% Glycerine  2%

The ingredients are mixed as a 45% slurry with water and wet milled to aparticle size of 4 microns, then spray-dried to remove water.

While the present invention has been set forth in specific andillustrative details and described with preferred particularity, it issusceptible to changes, modifications or alternations, obvious to one ofordinary skill in the art, without departing from the scope and spiritof the invention, which is defined by the claims appended hereto.

While the invention has been described in terms of various preferredembodiments, the skilled artisan will appreciate that variousmodifications, substitutions, omissions and changes can be made withoutdeparting from the spirit thereof. Accordingly, it is intended that thescope of the present invention be limited solely by the scope of thefollowing claims, including equivalents thereof.

What is claimed is:
 1. A compound having the formula:

wherein: X is —S(O)_(m)R₆, or R₇, Y is hydrogen, C-3 to C-6 alkenyl,alkynyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, halocycloalkylcarbonyl, aroyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl,haloalkylcarbonyl, aminoalkylcarbonyl, alkylaminoalkylcarbonyl,dialkylaminoalkylcarbonyl, alkoxyalkylcarbonyl, aryloxyalkylcarbonyl,alkylthioalkylcarbonyl, alkylsulfonylalkylcarbonyl,arylthioalkylcarbonyl, N-alkylcarbamoyl, N-arylcarbamoyl,N-alkylthiocarbamoyl, N-arylthiocarbamoyl,alpha-hydroxyarylalkylcarbonyl, hydroxyalkylcarbonyl,carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, —P(═O)(O-Alkyl)₂,—P(═S)(O-alkyl)₂, —P(═O)(S-alkyl)₂, —P(═S)(S-alkyl)₂, trialkylsilyl,alkylcarbonylaminoalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl,pyridinyl, pyrimidinyl, —C(═O)S-alkyl, —C(═O)S-aryl, —C(═O)S-alkylaryl,alkoxyalkoxycarbonyl, akylthioalkoxycarbonyl,alkylsulfonylalkoxycarbonyl, arylthioalkoxycarbonyl, alkoxycarbonyl,aryloxycarbonyl and aryloxycarbonylalkylcarbonyl; or alkyl or haloalkylboth of which are unsubstituted or substituted by alkoxy,alkoxycarbonyl, carboxy, cyano, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, alkylthio, nitro, alkylsulfinyl, alkylsulfonyl,alkylcarbonyl, amino, alkylamino, dialkylamino, hydroxy,alkylcarbonylamino or alkylcarbonyloxy; Z is hydrogen, halogen,—C(O)R₇—, —S(O)_(n)R₈, —C(O)OR₉, alkyl, haloalkyl, —OR₉, —N═C(R₁₀)(R₁₁),alkenyl, hydrazino, alkylthiocarbonyl, 1H-pyrrol-1-yl or1H-pyrazol-1-yl, —CHO, —CH═NOH, amino, R₁₂NH— or R₁₃R₁₄N—; R₁ ishydrogen, alkyl or —NR₁₅R₁₆; R₂ is hydrogen or halogen; R₃ and R₅ arehydrogen, halogen or alkyl; R₄ is halogen, haloalkyl, haloalkoxy,R₁₇S(O)_(p)— or SF₅; R₆ is alkyl or haloalkyl, alkenyl or haloalkenyl,alkynyl or haloalkynyl or cycloalkyl having 3 to 5 carbon atoms; R₇ isalkyl or haloalkyl; R₈ is R₇ or phenyl; R₉ and R₁₀ are hydrogen, alkylor haloalkyl: R₁₁ is alkyl, haloalkyl, alkoxy, or a phenyl group whichis unsubstituted or substituted by one or more groups selected fromhydroxy, halogen, alkoxy, cyano, R₇ or —S(O)_(q)R₇; R₁₂, R₁₃ and R₁₄,which are identical or different, are R₇S(O)_(r)—, formyl, alkynyl,alkoxycarbonyl, alkylthiocarbonyl or aroyl; or alkyl, C-3 to C-6 alkenylor —C(O)alkyl wherein the alkyl and alkenyl portions are unsubstitutedor substituted by one or more R₁₈; or R₁₃ and R₁₄ are joined so astogether form a divalent radical having 4 to 6 atoms in the chain, thisdivalent radical being alkylene, alkyleneoxyalkylene oralkyleneaminoalkylene; R₁₅ and R₁₆ are independently hydrogen or alkyl;R₁₇ is haloalkyl; R₁₈ is cyano, nitro, alkoxy, haloalkoxy, —C(O)R₇,R₈S(O)_(s)—, —C(O)OR₉, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, halogen, hydroxy, aminosulfonyl,alkylaminosulfonyl or dialkylaminosulfonyl; m, n, p, q, r and s areindependent of one another zero, one or two; M is C-halo, C—CH₃, C—CH₂F,C—CH₂Cl, C—NO₂, or N; or a geometric isomer, tautomeric form orpesticidally active salt thereof.
 2. A compound according to claim 1,wherein Z is amino, R₁₂NH— or R₁₃R₁₄N—.
 3. A compound according to claim1, wherein X is —S(O)_(m)R₆.
 4. A compound according to claim 1, whereinR₁ is amino or hydrogen.
 5. A compound according to claim 1, wherein R₆is alkyl.
 6. A compound according to claim 1, wherein R₆ is methyl orethyl.
 7. A compound according to claim 1, wherein R₃ and R₅ arehydrogen.
 8. A compound according to claim 1, wherein R₄ is haloalkyl,haloalkoxy or SF₅.
 9. A compound according to claim 1, wherein R₄ istrifluoromethyl.
 10. A compound according to claim 1, wherein M isC-halo, or N.
 11. A compound according to claim 1, wherein Y is hydrogenor alkoxycarbonyl.
 12. A compound of formula (I) according to claim 1,in which: X is —S(O)_(m)R₆; Y is hydrogen; alkyl having 1 to 4 carbonatoms, cycloalkyl having up to 4 carbons both of which are unsubstitutedor substituted by aminocarbonyl, alkylsulfonyl, alkoxy, alkoxycarbonyl,alkylcarbonyl, cyano or nitro; C-3 to C-4 alkenyl; C-3 to C-5 alkynyl;alkylcarbonyl; unsubstituted or substituted aroyl; arylalkylcarbonyl;alkylsulfonyl; alkoxycarbonylalkylcarbonyl; haloalkylcarbonyl;N-alkylcarbamoyl; alkoxycarbonyl; aryloxycarbonyl; alkoxyalkylcarbonyl;alpha-hydroxyarylalkylcarbonyl; hydroxyalkylcarbonyl;aminoalkylcarbonyl; —C(═O)S-alkyl and trialkylsilyl; Z is amino, R₁₂NH—,R₁₃R₁₄N—, halogen or methyl; R₁ is hydrogen, methyl, amino ormethylamino; R₂ is F, Cl, Br or H; R₃ and R₅ are hydrogen; R₄ is CF₃,CF₃O, CHF₂, CF₃S(O)_(p), CF₂Cl, CFCl₂, CF₂ClO, CFCl₂O, Cl, Br, or F; R₆is methyl or ethyl optionally substituted by F, Cl or Br; M is CCl, CF,CBr, or N; R₁₂, R₁₃ and R₁₄ are CF₃S(O)_(r)—, alkynyl or alkoxycarbonyl;or alkyl, C-3 to C-6 alkenyl or —C(O)alkyl wherein the alkyl and alkenylportions are unsubstituted or substituted by one or more R₁₈; and R₁₈ iscyano, nitro, alkoxy, haloalkoxy, C(O)R₇, R₈S(O)_(s)—, —C(O)OR₉,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, halogen,hydroxy, aminosulfonyl, alkyaminosulfonyl or dialkylaminosulfonyl.
 13. Acompound of formula (I) according to claim 1, in which: Y is hydrogen; aC₁ to C₃ alkyl group unsubstituted or substituted by cyano, carbamoyl,carboxy, alkoxycarbonyl, alkylthio, alkylsulfinyl or alkylsulfonyl;trialkylsilyl; acetyl; propionyl substituted by alkoxycarbonyl; benzoyloptionally substituted by alkyl; alkoxycarbonyl; or N-alkylcarbamoyl; Zis amino, R₁₂NH—, R₁₃R₁₄N—, —CHO, —CH═NOH, halogen or methyl; R₁ ishydrogen, methyl, amino or methylamino; R₂ is chlorine, bromine orhydrogen; R₃ and R₅ is hydrogen; R₄ is CF₃ or OCF₃; R₆ is optionallyhalogenated methyl or ethyl; R₇ is CF₃; R₁₂, R₁₃ and R₁₄ are alkynyl; ormethyl or ethyl optionally substituted by R₈S(O)_(s)—, cyano oraminocarbonyl; R₈ is alkyl or phenyl; and M is C—Cl, C—Br or N.
 14. Acompound according to claim 1, wherein the

group is: 2,6-dichloro-4-trifluoromethylphenyl;2,6-dichloro-4-trifluoromethoxyphenyl;2-bromo-6-chloro-4-trifluoromethylphenyl;2-bromo-6-chloro-4-trifluoromethoxyphenyl;2,6-difluoro-4-trifuoromethylphenyl; 2-chloro-4-trifluoromethylphenyl;3-chloro-5-trifluoromethyl-2-pyridinyl;3-chloro-5-trifluoromethoxy-2-pyridinyl;2-bromo-6-fluoro-4-difluoromethylphenyl;2-chloro-6-fluoro-4-trifluoromethylphenyl;2,6-dibromo-4-trifluoromethylphenyl;2,6-dibromo-4-trifluoromethoxyphenyl; or2,6-dichloro-4-pentafluorothiophenyl.
 15. The compound of formula (I)according to claim 1, which is:5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-difluoromethylthio-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehydeO-(methyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(acetyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(2-methylbenzoyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(methoxycarbonyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-[2-(ethoxycarbonyl)propionyl]oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehydeO-(acetyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehydeO-(methoxycarbonyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(methyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(N-methylcarbamoyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(carboxymethyl)oxime;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime:5-Amino-1-]2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(tert-butyldimethylsilyl)oxime;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-formyl-N-hydroxy-4-trifluoromethylthio-1H-pyrazole-3-carboximidamide;b1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-hydroxyiminomethyl-4-trifluoromethylthio-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(isopropyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(ethoxycarbonylmethyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(aminocarbonylmethyl)oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-[2-(ethylsulfonyl)ethyl]oxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeO-(2-cyanoethyl)oxime;1-[2,6-Dichlo-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carboxaldehydeoxime;1-[2,6-Dichlo-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime;1-[2,6-Dichloro(trifluoromethyl)phenyl]-5-methyl-4-methylsulfonyl-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-5-methyl-1H-pyrazole-3-carboxaldehydeoxime;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-methyl-1H-pyrazole-3-carboxaldehydeoxime:1-[2-Chloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyl)ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-dimethylamino-4-methylthio-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H-pyrazole-3-carboxaldehydeoxime;3-Acetyl-5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazoleoxime;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfinyl-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylthio-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboxidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfonyl-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylthio-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfonyl-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-N′-methyl-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-[2-(fluoroethyl)sulfinyl]-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-[2-(fluoroethyl)sulfonyl]-1H-pyrazole-3-carboximidamide;5-Amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-ethylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide;5-Amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-ethylamino-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyl)ethylamino]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;5-[2-(Cyano)ethylamino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;5-(Aminocarbonylmethylamino)-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-(phenylsulfonyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide;5-Amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide;1-[2-Bromo-6-chloro-4-(trifluoromethyl)phenyl]-5-ethylamino-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide;5-Amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboximidamide;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-(methylsulfinyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-(methylsulfinyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-(ethylsulfinyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide;1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[(prop-2-ynyl)amino]-N-hydroxy-1H-pyrazole-3-carboximidamide;and5-Amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide.16. A pesticidal composition comprising: (a) a compound of formula (I)

wherein: X is —S(O)_(m)R₆ or R₇, Y is hydrogen, C-3 to C-6 alkenyl,alkynyl, formyl, alkylcarbonyl, aroyl, arylalkylcarbonyl, alkylsulfonyl,arylsulfonyl, haloalkylcarbonyl, aminoalkylcarbonyl,alkylaminoalkylcarbonyl, dialkylaminoalkylcarbonyl, alkoxyalkylcarbonyl,aryloxyalkylcarbonyl, alkylthioalkylcarbonyl,alkylsulfonylalkylcarbonyl, arylthioalkylcarbonyl, N-alkylcarbamoyl,N-arylcarbamoyl, N-alkylthiocarbamoyl, N-arylthiocarbamoyl,alpha-hydroxyarylalkylcarbonyl, hydroxyalkylcarbonyl,carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, —P(═O)(O-Alkyl)₂,—P(═S)(O-alkyl)₂, —P(═O)(S-alkyl)₂, —P(═S)(S-alkyl)₂, trialkylsilyl,alkylcarbonylaminoalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl,pyridinyl, pyrimidinyl, —C(═O)S-alkyl, —C(═O)S-aryl, —C(═O)S-alkylaryl,alkoxyalkoxycarbonyl, alkylthioalkoxycarbonyl,alkylsulfonylalkoxycarbonyl, arylthioalkoxycarbonyl, alkoxycarbonyl,aryloxycarbonyl and aryloxycarbonylalkylcarbonyl; or alkyl or haloalkylboth of which are unsubstituted or substituted by alkoxy,alkoxycarbonyl, carboxy, cyano, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, alkylthio, nitro, alkylsulfinyl, alkylsulfonyl,alkylcarbonyl, amino, alkylamino, dialkylamino, hydroxy,alkylcarbonylamino or alkylcarbonyloxy; Z is hydrogen, halogen,—C(O)R₇—, —S(O)_(n)R₈, —C(O)OR₉, alkyl, haloalkyl, —OR₉, —N═C(R₁₀)(R₁₁),alkenyl, hydrazino, alkythiocarbonyl, 1H-pyrrol-1-yl or 1H-pyrazol-1-yl,—CHO, —CH═NOH, amino, R₁₂NH— or R₁₃R₁₄N—; R₁ is hydrogen, alkyl or—NR₁₅R₁₆; R₂ is hydrogen or halogen; R₃ and R₅ are hydrogen, halogen oralkyl; R₄ is halogen, haloalkyl, haloalkoxy, R₁₇S(O)_(p)— or SF₅; R₆ isalkyl or haloalkyl, alkenyl or haloalkenyl, alkynyl or haloalkynyl orcycloalkyl having 3 to 5 carbon atoms; R₇ is alkyl or haloalkyl; R₈ isR₇ or phenyl; R₉ and R₁₀ are hydrogen, alkyl or haloalkyl; R₁₁ is alkyl,haloalkyl, alkoxy, or a phenyl group which is unsubstituted orsubstituted by one or more groups selected from hydroxy, halogen,alkoxy, cyano, R₇ or —S(O)_(q)R₇; R₁₂, R₁₃ and R₁₄, which are identicalor different, are R₇S(O)_(r)—, formyl, alkynyl, alkoxycarbonyl,alkylthiocarbonyl or aroyl; or alkyl, C-3 to C-6 alkenyl or —C(O)alkylwherein the alkyl and alkenyl portions are unsubstituted or substitutedby one or more R₁₈; or R₁₃ and R₁₄ are joined so as together form adivalent radical having 4 to 6 atoms in the chain, this divalent radicalbeing alkylene, alkyleneoxyalkylene or alkyleneaminoalkylene; R₁₅ andR₁₆ are independently hydrogen or alkyl; R₁₇ is haloalkyl; R₁₈ is cyano,nitro, alkoxy, haloalkoxy, —C(O)R₇, R₈S(O)_(s)—, —C(O)OR₉,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, halogen,hydroxy, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl; p1m, n, p, q, r and s are independent of one another zero, one or two; Mis C-halo, C—CH₃, C—CH₂F, C—CH₂Cl, C—NO₂, or N; or a geometric isomer,tautomeric form or pesticidally active salt thereof; and (b) anagriculturally acceptable inert carrier therefor.
 17. A pesticidalcomposition according to claim 16 which has from about 0.05 to about 95%(by weight) of a compound of formula (I).
 18. A pesticidal compositionaccording to claim 16 which has from about 0.00005 to about 90% (byweight) of a compound of formula (I).